TY  - JOUR
AU  - Savić, Nevena
AU  - Markelić, Milica
AU  - Stančić, Ana
AU  - Veličković, Ksenija
AU  - Grigorov, Ilijana
AU  - Vučetić, Milica
AU  - Martinović, Vesna
AU  - Gudelj, Anđelija
AU  - Otašević, Vesna
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6627
AB  - Recently, we characterized the ferroptotic phenotype in the liver of diabetic
mice and revealed nuclear factor (erythroid-derived-2)-related factor 2 (Nrf2)
inactivation as an integral part of hepatic injury. Here, we aim to investigate
whether sulforaphane, an Nrf2 activator and antioxidant, prevents diabetes induced hepatic ferroptosis and the mechanisms involved. Male C57BL/6 mice
were divided into four groups: control (vehicle-treated), diabetic (streptozoto cin-induced; 40 mg/kg, from Days 1 to 5), diabetic sulforaphane-treated
(2.5 mg/kg from Days 1 to 42) and non-diabetic sulforaphane-treated group
(2.5 mg/kg from Days 1 to 42). Results showed that diabetes-induced inactiva tion of Nrf2 and decreased expression of its downstream antiferroptotic mole cules critical for antioxidative defense (catalase, superoxide dismutases,
thioredoxin reductase), iron metabolism (ferritin heavy chain (FTH1), ferro portin 1), glutathione (GSH) synthesis (cystine-glutamate antiporter system,
cystathionase, glutamate-cysteine ligase catalitic subunit, glutamate-cysteine
ligase modifier subunit, glutathione synthetase), and GSH recycling - glutathi one reductase (GR) were reversed/increased by sulforaphane treatment. In
addition, we found that the ferroptotic phenotype in diabetic liver is associated
with increased ferritinophagy and decreased FTH1 immunopositivity. The antiferroptotic effect of sulforaphane was further evidenced through the
increased level of GSH, decreased accumulation of labile iron and lipid perox ides (4-hydroxy-2-nonenal, lipofuscin), decreased ferritinophagy and liver dam age (decreased fibrosis, alanine aminotransferase, and aspartate
aminotransferase). Finally, diabetes-induced increase in serum glucose and tri glyceride level was significantly reduced by sulforaphane. Regardless of the fact
that this study is limited by the use of one model of experimentally induced
diabetes, the results obtained demonstrate for the first time that sulforaphane
prevents diabetes-induced hepatic ferroptosis in vivo through the activation of
Nrf2 signaling pathways. This nominates sulforaphane as a promising phytopharmaceutical for the prevention/alleviation of ferroptosis in diabetes-related
pathologies.
PB  - Hoboken: Wiley
T2  - BioFactors
T1  - Sulforaphane prevents diabetes-induced hepatic ferroptosis by activating Nrf2 signaling axis
DO  - 10.1002/biof.2042
ER  - 

@article{
author = "Savić, Nevena and Markelić, Milica and Stančić, Ana and Veličković, Ksenija and Grigorov, Ilijana and Vučetić, Milica and Martinović, Vesna and Gudelj, Anđelija and Otašević, Vesna",
year = "2024",
abstract = "Recently, we characterized the ferroptotic phenotype in the liver of diabetic
mice and revealed nuclear factor (erythroid-derived-2)-related factor 2 (Nrf2)
inactivation as an integral part of hepatic injury. Here, we aim to investigate
whether sulforaphane, an Nrf2 activator and antioxidant, prevents diabetes induced hepatic ferroptosis and the mechanisms involved. Male C57BL/6 mice
were divided into four groups: control (vehicle-treated), diabetic (streptozoto cin-induced; 40 mg/kg, from Days 1 to 5), diabetic sulforaphane-treated
(2.5 mg/kg from Days 1 to 42) and non-diabetic sulforaphane-treated group
(2.5 mg/kg from Days 1 to 42). Results showed that diabetes-induced inactiva tion of Nrf2 and decreased expression of its downstream antiferroptotic mole cules critical for antioxidative defense (catalase, superoxide dismutases,
thioredoxin reductase), iron metabolism (ferritin heavy chain (FTH1), ferro portin 1), glutathione (GSH) synthesis (cystine-glutamate antiporter system,
cystathionase, glutamate-cysteine ligase catalitic subunit, glutamate-cysteine
ligase modifier subunit, glutathione synthetase), and GSH recycling - glutathi one reductase (GR) were reversed/increased by sulforaphane treatment. In
addition, we found that the ferroptotic phenotype in diabetic liver is associated
with increased ferritinophagy and decreased FTH1 immunopositivity. The antiferroptotic effect of sulforaphane was further evidenced through the
increased level of GSH, decreased accumulation of labile iron and lipid perox ides (4-hydroxy-2-nonenal, lipofuscin), decreased ferritinophagy and liver dam age (decreased fibrosis, alanine aminotransferase, and aspartate
aminotransferase). Finally, diabetes-induced increase in serum glucose and tri glyceride level was significantly reduced by sulforaphane. Regardless of the fact
that this study is limited by the use of one model of experimentally induced
diabetes, the results obtained demonstrate for the first time that sulforaphane
prevents diabetes-induced hepatic ferroptosis in vivo through the activation of
Nrf2 signaling pathways. This nominates sulforaphane as a promising phytopharmaceutical for the prevention/alleviation of ferroptosis in diabetes-related
pathologies.",
publisher = "Hoboken: Wiley",
journal = "BioFactors",
title = "Sulforaphane prevents diabetes-induced hepatic ferroptosis by activating Nrf2 signaling axis",
doi = "10.1002/biof.2042"
}

Savić, N., Markelić, M., Stančić, A., Veličković, K., Grigorov, I., Vučetić, M., Martinović, V., Gudelj, A.,& Otašević, V.. (2024). Sulforaphane prevents diabetes-induced hepatic ferroptosis by activating Nrf2 signaling axis. in BioFactors
Hoboken: Wiley..
https://doi.org/10.1002/biof.2042

Savić N, Markelić M, Stančić A, Veličković K, Grigorov I, Vučetić M, Martinović V, Gudelj A, Otašević V. Sulforaphane prevents diabetes-induced hepatic ferroptosis by activating Nrf2 signaling axis. in BioFactors. 2024;.
doi:10.1002/biof.2042 .

Savić, Nevena, Markelić, Milica, Stančić, Ana, Veličković, Ksenija, Grigorov, Ilijana, Vučetić, Milica, Martinović, Vesna, Gudelj, Anđelija, Otašević, Vesna, "Sulforaphane prevents diabetes-induced hepatic ferroptosis by activating Nrf2 signaling axis" in BioFactors (2024),
https://doi.org/10.1002/biof.2042 . .

TY  - CONF
AU  - Veličković, Ksenija
AU  - Markelić, Milica
AU  - Stančić, Ana
AU  - Otašević, Vesna
AU  - Gudelj, Anđelija
AU  - Savić, Nevena
AU  - Martinović, Vesna
AU  - Grigorov, Ilijana
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6403
AB  - A high-sugar diet is associated with an increased risk of chronic intestinal disease1, but the capacity of the gut to adapt to dietary changes in young and adult rats is unknown. Therefore, the effects of an 8-week dextrose-enriched diet (20% or 60%) on intestinal histology, antioxidative defence status, and the expression pattern of high mobility group box-1 (HMGB1), a mediator of the inflammatory response2, were investigated. Numerous signs of tissue damage were associated with decreases in villus height (Vh), crypt depth (Cd), villus surface area (VSA), and muscle thickness (Mt) in adult rats fed with 60% dextrose. While the decrease in Vh and Cd was affected by age, the decrease in VSA and Mt was interactively affected by age and treatment. Structural changes were associated with decreased activity of antioxidative defence enzymes, particularly catalase, which is affected by treatment, and CuZnSOD, which is interactively modulated by age and treatment. Moreover, massive translocation of HMGB1 from the nucleus to the cytoplasm was detected in epithelial cells in the same group (interactive effect of age and treatment). We concluded that supraphysiological dextrose concentrations induce changes in the oxidative state, possibly leading to redox modification of HMGB1 and consequent tissue damage. The intestine undergoes dynamic functional and morphological changes with age that are more pronounced under high dextrose concentrations.
PB  - Belgrade: Faculty of Chemistry
C3  - Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia
T1  - Diet- and age-dependent changes of intestinal injury in rats
SP  - 80
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6403
ER  - 

@conference{
author = "Veličković, Ksenija and Markelić, Milica and Stančić, Ana and Otašević, Vesna and Gudelj, Anđelija and Savić, Nevena and Martinović, Vesna and Grigorov, Ilijana",
year = "2023",
abstract = "A high-sugar diet is associated with an increased risk of chronic intestinal disease1, but the capacity of the gut to adapt to dietary changes in young and adult rats is unknown. Therefore, the effects of an 8-week dextrose-enriched diet (20% or 60%) on intestinal histology, antioxidative defence status, and the expression pattern of high mobility group box-1 (HMGB1), a mediator of the inflammatory response2, were investigated. Numerous signs of tissue damage were associated with decreases in villus height (Vh), crypt depth (Cd), villus surface area (VSA), and muscle thickness (Mt) in adult rats fed with 60% dextrose. While the decrease in Vh and Cd was affected by age, the decrease in VSA and Mt was interactively affected by age and treatment. Structural changes were associated with decreased activity of antioxidative defence enzymes, particularly catalase, which is affected by treatment, and CuZnSOD, which is interactively modulated by age and treatment. Moreover, massive translocation of HMGB1 from the nucleus to the cytoplasm was detected in epithelial cells in the same group (interactive effect of age and treatment). We concluded that supraphysiological dextrose concentrations induce changes in the oxidative state, possibly leading to redox modification of HMGB1 and consequent tissue damage. The intestine undergoes dynamic functional and morphological changes with age that are more pronounced under high dextrose concentrations.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia",
title = "Diet- and age-dependent changes of intestinal injury in rats",
pages = "80",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6403"
}

Veličković, K., Markelić, M., Stančić, A., Otašević, V., Gudelj, A., Savić, N., Martinović, V.,& Grigorov, I.. (2023). Diet- and age-dependent changes of intestinal injury in rats. in Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia
Belgrade: Faculty of Chemistry., 80.
https://hdl.handle.net/21.15107/rcub_ibiss_6403

Veličković K, Markelić M, Stančić A, Otašević V, Gudelj A, Savić N, Martinović V, Grigorov I. Diet- and age-dependent changes of intestinal injury in rats. in Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia. 2023;:80.
https://hdl.handle.net/21.15107/rcub_ibiss_6403 .

Veličković, Ksenija, Markelić, Milica, Stančić, Ana, Otašević, Vesna, Gudelj, Anđelija, Savić, Nevena, Martinović, Vesna, Grigorov, Ilijana, "Diet- and age-dependent changes of intestinal injury in rats" in Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia (2023):80,
https://hdl.handle.net/21.15107/rcub_ibiss_6403 .

TY  - JOUR
AU  - Markelić, Milica
AU  - Stančić, Ana
AU  - Saksida, Tamara
AU  - Grigorov, Ilijana
AU  - Mićanović, Dragica
AU  - Veličković, Ksenija
AU  - Martinović, Vesna
AU  - Savić, Nevena
AU  - Gudelj, Anđelija
AU  - Otašević, Vesna
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6071
AB  - Introduction: Recently, the involvement of ferroptotic cell death in the reduction of β-cell mass in diabetes has been demonstrated. To elucidate the mechanisms of β-cell ferroptosis and potential antidiabetic effects of the ferroptosis inhibitor ferrostatin-1 (Fer-1) in vivo, a mouse model of type 1 diabetes (T1D) was used.

Methods: Animals were divided into three groups: control (vehicle-treated), diabetic (streptozotocin-treated, 40 mg/kg, from days 1-5), and diabetic treated with Fer-1 (1 mg/kg, from days 1-21). On day 22, glycemia and insulinemia were measured and pancreases were isolated for microscopic analyses.

Results: Diabetes disturbed general parameters of β-cell mass (islet size, β-cell abundance and distribution) and health (insulin and PDX-1 expression), increased lipid peroxidation in islet cells, and phagocytic removal of iron-containing material. It also downregulated the main players of the antiferroptotic pathway - Nrf2, GPX4, and xCT. In contrast, Fer-1 ameliorated the signs of deterioration of β-cell/islets, decreased lipid peroxidation, and reduced phagocytic activity, while upregulated expression of Nrf2 (and its nuclear translocation), GPX4, and xCT in β-cell/islets.

Discussion: Overall, our study confirms ferroptosis as an important mode of β-cell death in T1D and suggests antiferroptotic agents as a promising strategy for the prevention and treatment of diabetes
PB  - Lausanne: Frontiers Media SA
T2  - Frontiers in Endocrinology
T1  - Defining the ferroptotic phenotype of beta cells in type 1 diabetes and its inhibition as a potential antidiabetic strategy
VL  - 14
DO  - 10.3389/fendo.2023.1227498
SP  - 1227498
ER  - 

@article{
author = "Markelić, Milica and Stančić, Ana and Saksida, Tamara and Grigorov, Ilijana and Mićanović, Dragica and Veličković, Ksenija and Martinović, Vesna and Savić, Nevena and Gudelj, Anđelija and Otašević, Vesna",
year = "2023",
abstract = "Introduction: Recently, the involvement of ferroptotic cell death in the reduction of β-cell mass in diabetes has been demonstrated. To elucidate the mechanisms of β-cell ferroptosis and potential antidiabetic effects of the ferroptosis inhibitor ferrostatin-1 (Fer-1) in vivo, a mouse model of type 1 diabetes (T1D) was used.

Methods: Animals were divided into three groups: control (vehicle-treated), diabetic (streptozotocin-treated, 40 mg/kg, from days 1-5), and diabetic treated with Fer-1 (1 mg/kg, from days 1-21). On day 22, glycemia and insulinemia were measured and pancreases were isolated for microscopic analyses.

Results: Diabetes disturbed general parameters of β-cell mass (islet size, β-cell abundance and distribution) and health (insulin and PDX-1 expression), increased lipid peroxidation in islet cells, and phagocytic removal of iron-containing material. It also downregulated the main players of the antiferroptotic pathway - Nrf2, GPX4, and xCT. In contrast, Fer-1 ameliorated the signs of deterioration of β-cell/islets, decreased lipid peroxidation, and reduced phagocytic activity, while upregulated expression of Nrf2 (and its nuclear translocation), GPX4, and xCT in β-cell/islets.

Discussion: Overall, our study confirms ferroptosis as an important mode of β-cell death in T1D and suggests antiferroptotic agents as a promising strategy for the prevention and treatment of diabetes",
publisher = "Lausanne: Frontiers Media SA",
journal = "Frontiers in Endocrinology",
title = "Defining the ferroptotic phenotype of beta cells in type 1 diabetes and its inhibition as a potential antidiabetic strategy",
volume = "14",
doi = "10.3389/fendo.2023.1227498",
pages = "1227498"
}

Markelić, M., Stančić, A., Saksida, T., Grigorov, I., Mićanović, D., Veličković, K., Martinović, V., Savić, N., Gudelj, A.,& Otašević, V.. (2023). Defining the ferroptotic phenotype of beta cells in type 1 diabetes and its inhibition as a potential antidiabetic strategy. in Frontiers in Endocrinology
Lausanne: Frontiers Media SA., 14, 1227498.
https://doi.org/10.3389/fendo.2023.1227498

Markelić M, Stančić A, Saksida T, Grigorov I, Mićanović D, Veličković K, Martinović V, Savić N, Gudelj A, Otašević V. Defining the ferroptotic phenotype of beta cells in type 1 diabetes and its inhibition as a potential antidiabetic strategy. in Frontiers in Endocrinology. 2023;14:1227498.
doi:10.3389/fendo.2023.1227498 .

Markelić, Milica, Stančić, Ana, Saksida, Tamara, Grigorov, Ilijana, Mićanović, Dragica, Veličković, Ksenija, Martinović, Vesna, Savić, Nevena, Gudelj, Anđelija, Otašević, Vesna, "Defining the ferroptotic phenotype of beta cells in type 1 diabetes and its inhibition as a potential antidiabetic strategy" in Frontiers in Endocrinology, 14 (2023):1227498,
https://doi.org/10.3389/fendo.2023.1227498 . .

TY  - CONF
AU  - Stančić, Ana
AU  - Otašević, Vesna
AU  - Markelić, Milica
AU  - Veličković, Ksenija
AU  - Gudelj, Anđelija
AU  - Savić, Nevena
AU  - Martinović, Vesna
AU  - Grigorov, Ilijana
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6068
AB  - We showed recently that ferroptosis contributes to liver pathological changes in diabetes. So, targeting of ferroptosis-related pathways could be novel approach for treatment of diabetes- related liver diseases. Ethyl pyruvate (EP) showed antidiabetic action due to anti-oxidative, - inflammatory and -apoptotic properties. We aimed to examine its potential antiferroptotic action  in diabetes-related liver pathology.
Male Wistar rats were divided into four groups: control; diabetic (STZ, 65 mg/kg); diabetic pre- treated with EP (80 mg/kg/day, starting one week before STZ and continuing following 4  weeks) and diabetic treated with EP, starting with STZ and lasted 4   weeks.
Both modes of EP treatment induced attenuation of ferroptotic events in the liver of diabetic  rats: accumulation of lipid peroxides (4-HNE), disturbances in iron metabolism (decreased   FTH and increased TFR expression), decrease in expression level/activity of ferroptosis-  related antioxidative-defense molecules (GPX4, GCL, GSS, Nrf2, HO-1), and activation of ferroptosis-related pro-inflammatory events (HMGB1 nucleus-to-cytosol and NF-kB cytosol-to- nucleus translocation). Those changes reflected on the improvement of diabetes-related morphological alterations such as liver fibrosis and  binucleation.
Overall, EP interferes with ferroptosis signaling pathways and exerts antiferroptotic activity in the liver in diabetic state. This highlighting the significance of ferroptosis targeting in diabetes- related liver diseases and novel mechanisms/targets of EP beneficial   actions.
PB  - EMBO
C3  - EMBO Workshop: Ferroptosis: When metabolism meets cell death; 2023 Apr 23-27; Seeon, Germany
T1  - Antiferroptotic approach for the treatment of diabetes-induced liver pathology: the effects of ethyl pyruvate
SP  - 92
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6068
ER  - 

@conference{
author = "Stančić, Ana and Otašević, Vesna and Markelić, Milica and Veličković, Ksenija and Gudelj, Anđelija and Savić, Nevena and Martinović, Vesna and Grigorov, Ilijana",
year = "2023",
abstract = "We showed recently that ferroptosis contributes to liver pathological changes in diabetes. So, targeting of ferroptosis-related pathways could be novel approach for treatment of diabetes- related liver diseases. Ethyl pyruvate (EP) showed antidiabetic action due to anti-oxidative, - inflammatory and -apoptotic properties. We aimed to examine its potential antiferroptotic action  in diabetes-related liver pathology.
Male Wistar rats were divided into four groups: control; diabetic (STZ, 65 mg/kg); diabetic pre- treated with EP (80 mg/kg/day, starting one week before STZ and continuing following 4  weeks) and diabetic treated with EP, starting with STZ and lasted 4   weeks.
Both modes of EP treatment induced attenuation of ferroptotic events in the liver of diabetic  rats: accumulation of lipid peroxides (4-HNE), disturbances in iron metabolism (decreased   FTH and increased TFR expression), decrease in expression level/activity of ferroptosis-  related antioxidative-defense molecules (GPX4, GCL, GSS, Nrf2, HO-1), and activation of ferroptosis-related pro-inflammatory events (HMGB1 nucleus-to-cytosol and NF-kB cytosol-to- nucleus translocation). Those changes reflected on the improvement of diabetes-related morphological alterations such as liver fibrosis and  binucleation.
Overall, EP interferes with ferroptosis signaling pathways and exerts antiferroptotic activity in the liver in diabetic state. This highlighting the significance of ferroptosis targeting in diabetes- related liver diseases and novel mechanisms/targets of EP beneficial   actions.",
publisher = "EMBO",
journal = "EMBO Workshop: Ferroptosis: When metabolism meets cell death; 2023 Apr 23-27; Seeon, Germany",
title = "Antiferroptotic approach for the treatment of diabetes-induced liver pathology: the effects of ethyl pyruvate",
pages = "92",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6068"
}

Stančić, A., Otašević, V., Markelić, M., Veličković, K., Gudelj, A., Savić, N., Martinović, V.,& Grigorov, I.. (2023). Antiferroptotic approach for the treatment of diabetes-induced liver pathology: the effects of ethyl pyruvate. in EMBO Workshop: Ferroptosis: When metabolism meets cell death; 2023 Apr 23-27; Seeon, Germany
EMBO., 92.
https://hdl.handle.net/21.15107/rcub_ibiss_6068

Stančić A, Otašević V, Markelić M, Veličković K, Gudelj A, Savić N, Martinović V, Grigorov I. Antiferroptotic approach for the treatment of diabetes-induced liver pathology: the effects of ethyl pyruvate. in EMBO Workshop: Ferroptosis: When metabolism meets cell death; 2023 Apr 23-27; Seeon, Germany. 2023;:92.
https://hdl.handle.net/21.15107/rcub_ibiss_6068 .

Stančić, Ana, Otašević, Vesna, Markelić, Milica, Veličković, Ksenija, Gudelj, Anđelija, Savić, Nevena, Martinović, Vesna, Grigorov, Ilijana, "Antiferroptotic approach for the treatment of diabetes-induced liver pathology: the effects of ethyl pyruvate" in EMBO Workshop: Ferroptosis: When metabolism meets cell death; 2023 Apr 23-27; Seeon, Germany (2023):92,
https://hdl.handle.net/21.15107/rcub_ibiss_6068 .

TY  - CONF
AU  - Otašević, Vesna
AU  - Grigorov, Ilijana
AU  - Savić, Nevena
AU  - Markelić, Milica
AU  - Veličković, Ksenija
AU  - Gudelj, Anđelija
AU  - Martinović, Vesna
AU  - Stančić, Ana
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6067
AB  - Recently, we characterized the ferroptotic phenotype of the liver of diabetic mice and revealed the inactivation of Nrf2 as an integral part of diabetes-induced liver ferroptosis. We aim here to examine does sulforaphane, an Nrf2 activator and antioxidant, prevent diabetes-induced liver ferroptosis and the mechanisms  involved.
For that purpose, male C57BL/6 mice were divided into three groups: control, diabetic (streptozotocin-treated, 40 mg/kg/5 consecutive days), diabetic+sulforaphane treated (2.5 mg/kg, from day 1-42).
Results showed that diabetes-induced inactivation of Nrf2 and decreased expression of its downstream antiferroptotic parameters crucial for antioxidative defense (HO-1, catalase, SOD), iron metabolism (ferroportin, ferritin), glutathione synthesis (xCT, GCLC, CTH, CBS) and recycling (GR) were reversed/increased by sulforaphane treatment. Antiferroptotic effect of sulforaphane in the diabetic liver was further evidenced through the increased level of glutathione, decreased accumulation of liable iron and lipid peroxides (4-HNE) and decreased tissue damage (fibrosis and infiltration). Finally, diabetes-induced increase in serum glucose, ALT, AST and triglyceride level was significantly reduced by   sulforaphane.
These findings revealed for the first time that sulforaphane prevents in vivo diabetes-induced liver ferroptosis through activation of Nrf2 signaling axis. This suggests sulforaphane as a promising therapeutic tool for preventing ferroptosis at least in diabetes and diabetes-related pathologies.
PB  - EMBO
C3  - EMBO Workshop: Ferroptosis: When metabolism meets cell death; 2023 Apr 23-27; Seeon, Germany
T1  - Sulforaphane prevents diabetes-induced liver ferroptosis through activation of Nrf2 signaling axis
SP  - 91
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6067
ER  - 

@conference{
author = "Otašević, Vesna and Grigorov, Ilijana and Savić, Nevena and Markelić, Milica and Veličković, Ksenija and Gudelj, Anđelija and Martinović, Vesna and Stančić, Ana",
year = "2023",
abstract = "Recently, we characterized the ferroptotic phenotype of the liver of diabetic mice and revealed the inactivation of Nrf2 as an integral part of diabetes-induced liver ferroptosis. We aim here to examine does sulforaphane, an Nrf2 activator and antioxidant, prevent diabetes-induced liver ferroptosis and the mechanisms  involved.
For that purpose, male C57BL/6 mice were divided into three groups: control, diabetic (streptozotocin-treated, 40 mg/kg/5 consecutive days), diabetic+sulforaphane treated (2.5 mg/kg, from day 1-42).
Results showed that diabetes-induced inactivation of Nrf2 and decreased expression of its downstream antiferroptotic parameters crucial for antioxidative defense (HO-1, catalase, SOD), iron metabolism (ferroportin, ferritin), glutathione synthesis (xCT, GCLC, CTH, CBS) and recycling (GR) were reversed/increased by sulforaphane treatment. Antiferroptotic effect of sulforaphane in the diabetic liver was further evidenced through the increased level of glutathione, decreased accumulation of liable iron and lipid peroxides (4-HNE) and decreased tissue damage (fibrosis and infiltration). Finally, diabetes-induced increase in serum glucose, ALT, AST and triglyceride level was significantly reduced by   sulforaphane.
These findings revealed for the first time that sulforaphane prevents in vivo diabetes-induced liver ferroptosis through activation of Nrf2 signaling axis. This suggests sulforaphane as a promising therapeutic tool for preventing ferroptosis at least in diabetes and diabetes-related pathologies.",
publisher = "EMBO",
journal = "EMBO Workshop: Ferroptosis: When metabolism meets cell death; 2023 Apr 23-27; Seeon, Germany",
title = "Sulforaphane prevents diabetes-induced liver ferroptosis through activation of Nrf2 signaling axis",
pages = "91",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6067"
}

Otašević, V., Grigorov, I., Savić, N., Markelić, M., Veličković, K., Gudelj, A., Martinović, V.,& Stančić, A.. (2023). Sulforaphane prevents diabetes-induced liver ferroptosis through activation of Nrf2 signaling axis. in EMBO Workshop: Ferroptosis: When metabolism meets cell death; 2023 Apr 23-27; Seeon, Germany
EMBO., 91.
https://hdl.handle.net/21.15107/rcub_ibiss_6067

Otašević V, Grigorov I, Savić N, Markelić M, Veličković K, Gudelj A, Martinović V, Stančić A. Sulforaphane prevents diabetes-induced liver ferroptosis through activation of Nrf2 signaling axis. in EMBO Workshop: Ferroptosis: When metabolism meets cell death; 2023 Apr 23-27; Seeon, Germany. 2023;:91.
https://hdl.handle.net/21.15107/rcub_ibiss_6067 .

Otašević, Vesna, Grigorov, Ilijana, Savić, Nevena, Markelić, Milica, Veličković, Ksenija, Gudelj, Anđelija, Martinović, Vesna, Stančić, Ana, "Sulforaphane prevents diabetes-induced liver ferroptosis through activation of Nrf2 signaling axis" in EMBO Workshop: Ferroptosis: When metabolism meets cell death; 2023 Apr 23-27; Seeon, Germany (2023):91,
https://hdl.handle.net/21.15107/rcub_ibiss_6067 .

TY  - CONF
AU  - Savić, Nevena
AU  - Otašević, Vesna
AU  - Saksida, Tamara
AU  - Markelić, Milica
AU  - Grigorov, Ilijana
AU  - Veličković, Ksenija
AU  - Martinović, Vesna
AU  - Mićanović, Dragica
AU  - Ivanović, Anđelija
AU  - Stančić, Ana
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5195
AB  - Један од узрока патолошких промена јетре током Diabetes mellitus-a (ДМ) јесте повећање ћелијске смрти. До данас је описана апоптоза, некроза и аутофагија хепатоцита.1 Циљ ове студије био је испитивање укључености фероптозе, ћелијске смрти која настаје услед интезивираног процеса липидне пероксидације зависне од гвожђа, на развој патолошких промена јетре у ДМ, коришћењем фероптотског инхибитора феростатина-1 (Фер-1). Мужјаци C57BL/6 мишева подељени су у три групе: 1. контрола (К); 2. дијабетeс (индукован стрептозотоцином, Д) и 3. дијабетес + Фер-1 (ДФ). У групи Д забележена је смањена експресија цитопротективног транскрипционог фактора Nrf2 (енгл. nuclear factor (erythroid-derived-2)-related factor2), што је случај и са његовим таргетним протеинима битним за регулисање процеса фероптозе, као што су кључни ензим за уклањање липидних пероксида, GPx4 (глутатион пероксидаза 4), цистеин-глутаматни трансмембрански антипортер (xCT) укључен у регулацију метаболизма глутатиона и хем оксигеназа 1 (HO-1) која регулише метаболизам гвожђа. У групи ДФ забележено је значајно повећање експресије Nrf2, GPx4, xCT и HO-1. Маркер липидне пероксидације 4-HNE повећан је у хепатоцитима Д групе, а смањен у ДФ групи. Наши резултати показују да хепатоцити у ДМ подлежу фероптози, с обзиром на чињеницу да Фер-1 делује цитопротективно, активирајући Nrf2-зависну сигналну каскаду. Ово нас упућује на фероптозу као нову терапеутску мету у лечењу патолошких промена јетре у ДМ и то стимулисаном активацијом Nrf2.
AB  - Jedan od uzroka patoloških promena jetre tokom Diabetes mellitus-a (DM) jeste povećanje ćelijske smrti. Do danas je opisana apoptoza, nekroza i autofagija hepatocita.1 Cilj ove studije bio je ispitivanje uključenosti feroptoze, ćelijske smrti koja nastaje usled inteziviranog procesa lipidne peroksidacije zavisne od gvožđa, na razvoj patoloških promena jetre u DM, korišćenjem feroptotskog inhibitora ferostatina-1 (Fer-1). Mužjaci C57BL/6 miševa podeljeni su u tri grupe: 1. kontrola (K); 2. dijabetes (indukovan streptozotocinom, D) i 3. dijabetes + Fer-1 (DF). U grupi D zabeležena je smanjena ekspresija citoprotektivnog transkripcionog faktora Nrf2 (engl. nuclear factor (erythroid-derived-2)-related factor2), što je slučaj i sa njegovim targetnim proteinima bitnim za regulisanje procesa feroptoze, kao što su ključni enzim za uklanjanje lipidnih peroksida, GPx4 (glutation peroksidaza 4), cistein-glutamatni transmembranski antiporter (xCT) uključen u regulaciju metabolizma glutationa i hem oksigenaza 1 (HO-1) koja reguliše metabolizam gvožđa. U grupi DF zabeleženo je značajno povećanje ekspresije Nrf2, GPx4, xCT i HO-1. Marker lipidne peroksidacije 4-HNE povećan je u hepatocitima D grupe, a smanjen u DF grupi. Naši rezultati pokazuju da hepatociti u DM podležu feroptozi, s obzirom na činjenicu da Fer-1 deluje citoprotektivno, aktivirajući Nrf2-zavisnu signalnu kaskadu. Ovo nas upućuje na feroptozu kao novu terapeutsku metu u lečenju patoloških promena jetre u DM i to stimulisanom aktivacijom Nrf2.
PB  - Belgrade: Serbian Biological Society
C3  - Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
T1  - Допринос фероптозе патолошким променама јетре дијабетичних мишева
T1  - Doprinos feroptoze patološkim promenama jetre dijabetičnih miševa
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5195
ER  - 

@conference{
author = "Savić, Nevena and Otašević, Vesna and Saksida, Tamara and Markelić, Milica and Grigorov, Ilijana and Veličković, Ksenija and Martinović, Vesna and Mićanović, Dragica and Ivanović, Anđelija and Stančić, Ana",
year = "2022",
abstract = "Један од узрока патолошких промена јетре током Diabetes mellitus-a (ДМ) јесте повећање ћелијске смрти. До данас је описана апоптоза, некроза и аутофагија хепатоцита.1 Циљ ове студије био је испитивање укључености фероптозе, ћелијске смрти која настаје услед интезивираног процеса липидне пероксидације зависне од гвожђа, на развој патолошких промена јетре у ДМ, коришћењем фероптотског инхибитора феростатина-1 (Фер-1). Мужјаци C57BL/6 мишева подељени су у три групе: 1. контрола (К); 2. дијабетeс (индукован стрептозотоцином, Д) и 3. дијабетес + Фер-1 (ДФ). У групи Д забележена је смањена експресија цитопротективног транскрипционог фактора Nrf2 (енгл. nuclear factor (erythroid-derived-2)-related factor2), што је случај и са његовим таргетним протеинима битним за регулисање процеса фероптозе, као што су кључни ензим за уклањање липидних пероксида, GPx4 (глутатион пероксидаза 4), цистеин-глутаматни трансмембрански антипортер (xCT) укључен у регулацију метаболизма глутатиона и хем оксигеназа 1 (HO-1) која регулише метаболизам гвожђа. У групи ДФ забележено је значајно повећање експресије Nrf2, GPx4, xCT и HO-1. Маркер липидне пероксидације 4-HNE повећан је у хепатоцитима Д групе, а смањен у ДФ групи. Наши резултати показују да хепатоцити у ДМ подлежу фероптози, с обзиром на чињеницу да Фер-1 делује цитопротективно, активирајући Nrf2-зависну сигналну каскаду. Ово нас упућује на фероптозу као нову терапеутску мету у лечењу патолошких промена јетре у ДМ и то стимулисаном активацијом Nrf2., Jedan od uzroka patoloških promena jetre tokom Diabetes mellitus-a (DM) jeste povećanje ćelijske smrti. Do danas je opisana apoptoza, nekroza i autofagija hepatocita.1 Cilj ove studije bio je ispitivanje uključenosti feroptoze, ćelijske smrti koja nastaje usled inteziviranog procesa lipidne peroksidacije zavisne od gvožđa, na razvoj patoloških promena jetre u DM, korišćenjem feroptotskog inhibitora ferostatina-1 (Fer-1). Mužjaci C57BL/6 miševa podeljeni su u tri grupe: 1. kontrola (K); 2. dijabetes (indukovan streptozotocinom, D) i 3. dijabetes + Fer-1 (DF). U grupi D zabeležena je smanjena ekspresija citoprotektivnog transkripcionog faktora Nrf2 (engl. nuclear factor (erythroid-derived-2)-related factor2), što je slučaj i sa njegovim targetnim proteinima bitnim za regulisanje procesa feroptoze, kao što su ključni enzim za uklanjanje lipidnih peroksida, GPx4 (glutation peroksidaza 4), cistein-glutamatni transmembranski antiporter (xCT) uključen u regulaciju metabolizma glutationa i hem oksigenaza 1 (HO-1) koja reguliše metabolizam gvožđa. U grupi DF zabeleženo je značajno povećanje ekspresije Nrf2, GPx4, xCT i HO-1. Marker lipidne peroksidacije 4-HNE povećan je u hepatocitima D grupe, a smanjen u DF grupi. Naši rezultati pokazuju da hepatociti u DM podležu feroptozi, s obzirom na činjenicu da Fer-1 deluje citoprotektivno, aktivirajući Nrf2-zavisnu signalnu kaskadu. Ovo nas upućuje na feroptozu kao novu terapeutsku metu u lečenju patoloških promena jetre u DM i to stimulisanom aktivacijom Nrf2.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia",
title = "Допринос фероптозе патолошким променама јетре дијабетичних мишева, Doprinos feroptoze patološkim promenama jetre dijabetičnih miševa",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5195"
}

Savić, N., Otašević, V., Saksida, T., Markelić, M., Grigorov, I., Veličković, K., Martinović, V., Mićanović, D., Ivanović, A.,& Stančić, A.. (2022). Допринос фероптозе патолошким променама јетре дијабетичних мишева. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
Belgrade: Serbian Biological Society..
https://hdl.handle.net/21.15107/rcub_ibiss_5195

Savić N, Otašević V, Saksida T, Markelić M, Grigorov I, Veličković K, Martinović V, Mićanović D, Ivanović A, Stančić A. Допринос фероптозе патолошким променама јетре дијабетичних мишева. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia. 2022;.
https://hdl.handle.net/21.15107/rcub_ibiss_5195 .

Savić, Nevena, Otašević, Vesna, Saksida, Tamara, Markelić, Milica, Grigorov, Ilijana, Veličković, Ksenija, Martinović, Vesna, Mićanović, Dragica, Ivanović, Anđelija, Stančić, Ana, "Допринос фероптозе патолошким променама јетре дијабетичних мишева" in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia (2022),
https://hdl.handle.net/21.15107/rcub_ibiss_5195 .

TY  - CONF
AU  - Otašević, Vesna
AU  - Saksida, Tamara
AU  - Markelić, Milica
AU  - Grigorov, Ilijana
AU  - Vučetić, Milica
AU  - Veličković, Ksenija
AU  - Martinović, Vesna
AU  - Mićanović, Dragica
AU  - Ivanović, Anđelija
AU  - Savić, Nevena
AU  - Stančić, Ana
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5197
AB  - Кључни патолошки догађај у настанку дијабетеса је губитак функционалних β-ћелија. Улога фероптозе, новоописаног типа регулисане ћелијске смрти зависне од гвожђа, у смањењу популације β-ћелија код дијабетеса није довољно испитана. Стога је у овом раду испитиван допринос фероптозе умирању β-ћелија у дијабетичним условима in vivo и in vitro. Код мишева са дијабетесом индукованим стрептозотоцином, СТЗ забележено је значајно повећање инфилтрације макрофага и акумулације липидних пероксида у острвцима панкреаса, праћено смањењем популације инсулин позитивних ћелија, експресије глутатион пероксидазе 4, GPX4, цистеин/глутамат транспортера xCT и хем оксигеназе 1. Резултати добијени in vitro на Rin-5f β-ћелијама су показали да дијабетични услови (висока концентрација глукозе, СТЗ, цитокини и водоник пероксид снижавају експресију транскрипционог фактора Nrf2, GPX4 и митохондријални мембрански потенцијал, а повећавају продукцију реактивних врста кисеоника, акумулацију слободног гвожђа, липидних пероксида и смртност β-ћелија. Примена инхибитора фероптозе, феростатина-1 у потпуности је поништила наведене промене, тј. остварила позитивне ефекте на β-ћелије/панкреас дијабетичних животиња, осим у случају in vitro третмана цитокинима, указујући на разлике између дијабетогених стимулуса у одређивању судбине β-ћелија. Наведени резултати показују да модулирање тј. инхибиција фероптозе у дијабетесу може бити нови обећавајући приступ за очување популације β-ћелија и третман дијабетеса.
AB  - Ključni patološki događaj u nastanku dijabetesa je gubitak funkcionalnih β-ćelija. Uloga feroptoze, novoopisanog tipa regulisane ćelijske smrti zavisne od gvožđa, u smanjenju populacije β-ćelija kod dijabetesa nije dovoljno ispitana. Stoga je u ovom radu ispitivan doprinos feroptoze umiranju β-ćelija u dijabetičnim uslovima in vivo i in vitro. Kod miševa sa dijabetesom indukovanim streptozotocinom, STZ zabeleženo je značajno povećanje infiltracije makrofaga i akumulacije lipidnih peroksida u ostrvcima pankreasa, praćeno smanjenjem populacije insulin pozitivnih ćelija, ekspresije glutation peroksidaze 4, GPX4, cistein/glutamat transportera xCT i hem oksigenaze 1. Rezultati dobijeni in vitro na Rin-5f β-ćelijama su pokazali da dijabetični uslovi (visoka koncentracija glukoze, STZ, citokini i vodonik peroksid snižavaju ekspresiju transkripcionog faktora Nrf2, GPX4 i mitohondrijalni membranski potencijal, a povećavaju produkciju reaktivnih vrsta kiseonika, akumulaciju slobodnog gvožđa, lipidnih peroksida i smrtnost β-ćelija. Primena inhibitora feroptoze, ferostatina-1 u potpunosti je poništila navedene promene, tj. ostvarila pozitivne efekte na β-ćelije/pankreas dijabetičnih životinja, osim u slučaju in vitro tretmana citokinima, ukazujući na razlike između dijabetogenih stimulusa u određivanju sudbine β-ćelija. Navedeni rezultati pokazuju da moduliranje tj. inhibicija feroptoze u dijabetesu može biti novi obećavajući pristup za očuvanje populacije β-ćelija i tretman dijabetesa.
PB  - Belgrade: Serbian Biological Society
C3  - Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
T1  - Фероптоза у дијабетесу и дијабетичним компликацијама
T1  - Feroptoza u dijabetesu i dijabetičnim komplikacijama
SP  - 279
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5197
ER  - 

@conference{
author = "Otašević, Vesna and Saksida, Tamara and Markelić, Milica and Grigorov, Ilijana and Vučetić, Milica and Veličković, Ksenija and Martinović, Vesna and Mićanović, Dragica and Ivanović, Anđelija and Savić, Nevena and Stančić, Ana",
year = "2022",
abstract = "Кључни патолошки догађај у настанку дијабетеса је губитак функционалних β-ћелија. Улога фероптозе, новоописаног типа регулисане ћелијске смрти зависне од гвожђа, у смањењу популације β-ћелија код дијабетеса није довољно испитана. Стога је у овом раду испитиван допринос фероптозе умирању β-ћелија у дијабетичним условима in vivo и in vitro. Код мишева са дијабетесом индукованим стрептозотоцином, СТЗ забележено је значајно повећање инфилтрације макрофага и акумулације липидних пероксида у острвцима панкреаса, праћено смањењем популације инсулин позитивних ћелија, експресије глутатион пероксидазе 4, GPX4, цистеин/глутамат транспортера xCT и хем оксигеназе 1. Резултати добијени in vitro на Rin-5f β-ћелијама су показали да дијабетични услови (висока концентрација глукозе, СТЗ, цитокини и водоник пероксид снижавају експресију транскрипционог фактора Nrf2, GPX4 и митохондријални мембрански потенцијал, а повећавају продукцију реактивних врста кисеоника, акумулацију слободног гвожђа, липидних пероксида и смртност β-ћелија. Примена инхибитора фероптозе, феростатина-1 у потпуности је поништила наведене промене, тј. остварила позитивне ефекте на β-ћелије/панкреас дијабетичних животиња, осим у случају in vitro третмана цитокинима, указујући на разлике између дијабетогених стимулуса у одређивању судбине β-ћелија. Наведени резултати показују да модулирање тј. инхибиција фероптозе у дијабетесу може бити нови обећавајући приступ за очување популације β-ћелија и третман дијабетеса., Ključni patološki događaj u nastanku dijabetesa je gubitak funkcionalnih β-ćelija. Uloga feroptoze, novoopisanog tipa regulisane ćelijske smrti zavisne od gvožđa, u smanjenju populacije β-ćelija kod dijabetesa nije dovoljno ispitana. Stoga je u ovom radu ispitivan doprinos feroptoze umiranju β-ćelija u dijabetičnim uslovima in vivo i in vitro. Kod miševa sa dijabetesom indukovanim streptozotocinom, STZ zabeleženo je značajno povećanje infiltracije makrofaga i akumulacije lipidnih peroksida u ostrvcima pankreasa, praćeno smanjenjem populacije insulin pozitivnih ćelija, ekspresije glutation peroksidaze 4, GPX4, cistein/glutamat transportera xCT i hem oksigenaze 1. Rezultati dobijeni in vitro na Rin-5f β-ćelijama su pokazali da dijabetični uslovi (visoka koncentracija glukoze, STZ, citokini i vodonik peroksid snižavaju ekspresiju transkripcionog faktora Nrf2, GPX4 i mitohondrijalni membranski potencijal, a povećavaju produkciju reaktivnih vrsta kiseonika, akumulaciju slobodnog gvožđa, lipidnih peroksida i smrtnost β-ćelija. Primena inhibitora feroptoze, ferostatina-1 u potpunosti je poništila navedene promene, tj. ostvarila pozitivne efekte na β-ćelije/pankreas dijabetičnih životinja, osim u slučaju in vitro tretmana citokinima, ukazujući na razlike između dijabetogenih stimulusa u određivanju sudbine β-ćelija. Navedeni rezultati pokazuju da moduliranje tj. inhibicija feroptoze u dijabetesu može biti novi obećavajući pristup za očuvanje populacije β-ćelija i tretman dijabetesa.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia",
title = "Фероптоза у дијабетесу и дијабетичним компликацијама, Feroptoza u dijabetesu i dijabetičnim komplikacijama",
pages = "279",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5197"
}

Otašević, V., Saksida, T., Markelić, M., Grigorov, I., Vučetić, M., Veličković, K., Martinović, V., Mićanović, D., Ivanović, A., Savić, N.,& Stančić, A.. (2022). Фероптоза у дијабетесу и дијабетичним компликацијама. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
Belgrade: Serbian Biological Society., 279.
https://hdl.handle.net/21.15107/rcub_ibiss_5197

Otašević V, Saksida T, Markelić M, Grigorov I, Vučetić M, Veličković K, Martinović V, Mićanović D, Ivanović A, Savić N, Stančić A. Фероптоза у дијабетесу и дијабетичним компликацијама. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia. 2022;:279.
https://hdl.handle.net/21.15107/rcub_ibiss_5197 .

Otašević, Vesna, Saksida, Tamara, Markelić, Milica, Grigorov, Ilijana, Vučetić, Milica, Veličković, Ksenija, Martinović, Vesna, Mićanović, Dragica, Ivanović, Anđelija, Savić, Nevena, Stančić, Ana, "Фероптоза у дијабетесу и дијабетичним компликацијама" in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia (2022):279,
https://hdl.handle.net/21.15107/rcub_ibiss_5197 .

TY  - JOUR
AU  - Stančić, Ana
AU  - Saksida, Tamara
AU  - Markelić, Milica
AU  - Vučetić, Milica
AU  - Grigorov, Ilijana
AU  - Martinović, Vesna
AU  - Mićanović, Dragica
AU  - Ivanović, Anđelija
AU  - Veličković, Ksenija
AU  - Savić, Nevena
AU  - Otašević, Vesna
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4910
AB  - The main pathological hallmark of diabetes is the loss of functional β-cells. Among several types of β-cell death in diabetes, the
involvement of ferroptosis remains elusive. Therefore, we investigated the potential of diabetes-mimicking factors: high glucose
(HG), proinflammatory cytokines, hydrogen peroxide (H2O2), or diabetogenic agent streptozotocin (STZ) to induce ferroptosis
of β-cells in vitro. Furthermore, we tested the contribution of ferroptosis to injury of pancreatic islets in an STZ-induced
in vivo diabetic model. All in vitro treatments increased loss of Rin-5F cells along with the accumulation of reactive oxygen
species, lipid peroxides and iron, inactivation of NF-E2-related factor 2 (Nrf2), and decrease in glutathione peroxidase 4
expression and mitochondrial membrane potential (MMP). Ferrostatin 1 (Fer-1), ferroptosis inhibitor, diminished the abovestated effects and rescued cells from death in case of HG, STZ, and H2O2 treatments, while failed to increase MMP and to
attenuate cell death after the cytokines’ treatment. Moreover, Fer-1 protected pancreatic islets from STZ-induced injury in
diabetic in vivo model, since it decreased infiltration of macrophages and accumulation of lipid peroxides and increased the
population of insulin-positive cells. Such results revealed differences between diabetogenic stimuli in determining the destiny of
β-cells, emerging HG, H2O2, and STZ, but not cytokines, as contributing factors to ferroptosis and shed new light on an
antidiabetic strategy based on Nrf2 activation. Thus, targeting ferroptosis in diabetes might be a promising new approach for
preservation of the β-cell population. Our results obtained from in vivo study strongly justify this approach.
PB  - London:Hindawi
T2  - Oxidative Medicine and Cellular Longevity
T1  - Ferroptosis as a Novel Determinant of β-Cell Death in Diabetic Conditions
VL  - 2022
DO  - 10.1155/2022/3873420
SP  - 3873420
ER  - 

@article{
author = "Stančić, Ana and Saksida, Tamara and Markelić, Milica and Vučetić, Milica and Grigorov, Ilijana and Martinović, Vesna and Mićanović, Dragica and Ivanović, Anđelija and Veličković, Ksenija and Savić, Nevena and Otašević, Vesna",
year = "2022",
abstract = "The main pathological hallmark of diabetes is the loss of functional β-cells. Among several types of β-cell death in diabetes, the
involvement of ferroptosis remains elusive. Therefore, we investigated the potential of diabetes-mimicking factors: high glucose
(HG), proinflammatory cytokines, hydrogen peroxide (H2O2), or diabetogenic agent streptozotocin (STZ) to induce ferroptosis
of β-cells in vitro. Furthermore, we tested the contribution of ferroptosis to injury of pancreatic islets in an STZ-induced
in vivo diabetic model. All in vitro treatments increased loss of Rin-5F cells along with the accumulation of reactive oxygen
species, lipid peroxides and iron, inactivation of NF-E2-related factor 2 (Nrf2), and decrease in glutathione peroxidase 4
expression and mitochondrial membrane potential (MMP). Ferrostatin 1 (Fer-1), ferroptosis inhibitor, diminished the abovestated effects and rescued cells from death in case of HG, STZ, and H2O2 treatments, while failed to increase MMP and to
attenuate cell death after the cytokines’ treatment. Moreover, Fer-1 protected pancreatic islets from STZ-induced injury in
diabetic in vivo model, since it decreased infiltration of macrophages and accumulation of lipid peroxides and increased the
population of insulin-positive cells. Such results revealed differences between diabetogenic stimuli in determining the destiny of
β-cells, emerging HG, H2O2, and STZ, but not cytokines, as contributing factors to ferroptosis and shed new light on an
antidiabetic strategy based on Nrf2 activation. Thus, targeting ferroptosis in diabetes might be a promising new approach for
preservation of the β-cell population. Our results obtained from in vivo study strongly justify this approach.",
publisher = "London:Hindawi",
journal = "Oxidative Medicine and Cellular Longevity",
title = "Ferroptosis as a Novel Determinant of β-Cell Death in Diabetic Conditions",
volume = "2022",
doi = "10.1155/2022/3873420",
pages = "3873420"
}

Stančić, A., Saksida, T., Markelić, M., Vučetić, M., Grigorov, I., Martinović, V., Mićanović, D., Ivanović, A., Veličković, K., Savić, N.,& Otašević, V.. (2022). Ferroptosis as a Novel Determinant of β-Cell Death in Diabetic Conditions. in Oxidative Medicine and Cellular Longevity
London:Hindawi., 2022, 3873420.
https://doi.org/10.1155/2022/3873420

Stančić A, Saksida T, Markelić M, Vučetić M, Grigorov I, Martinović V, Mićanović D, Ivanović A, Veličković K, Savić N, Otašević V. Ferroptosis as a Novel Determinant of β-Cell Death in Diabetic Conditions. in Oxidative Medicine and Cellular Longevity. 2022;2022:3873420.
doi:10.1155/2022/3873420 .

Stančić, Ana, Saksida, Tamara, Markelić, Milica, Vučetić, Milica, Grigorov, Ilijana, Martinović, Vesna, Mićanović, Dragica, Ivanović, Anđelija, Veličković, Ksenija, Savić, Nevena, Otašević, Vesna, "Ferroptosis as a Novel Determinant of β-Cell Death in Diabetic Conditions" in Oxidative Medicine and Cellular Longevity, 2022 (2022):3873420,
https://doi.org/10.1155/2022/3873420 . .

TY  - JOUR
AU  - Stančić, Ana
AU  - Veličković, Ksenija
AU  - Markelić, Milica
AU  - Grigorov, Ilijana
AU  - Saksida, Tamara
AU  - Savić, Nevena
AU  - Vučetić, Milica
AU  - Martinović, Vesna
AU  - Ivanović, Anđelija
AU  - Otašević, Vesna
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5160
AB  - Cell death plays an important role in diabetes-induced liver dysfunction. Ferroptosis is a
newly defined regulated cell death caused by iron-dependent lipid peroxidation. Our previous studies
have shown that high glucose and streptozotocin (STZ) cause  -cell death through ferroptosis and
that ferrostatin-1 (Fer-1), an inhibitor of ferroptosis, improves  -cell viability, islet morphology, and
function. This study was aimed to examine in vivo the involvement of ferroptosis in diabetes-related
pathological changes in the liver. For this purpose, male C57BL/6 mice, in which diabetes was induced
with STZ (40 mg/kg/5 consecutive days), were treated with Fer-1 (1 mg/kg, from day 1–21 day). It
was found that in diabetic mice Fer-1 improved serum levels of ALT and triglycerides and decreased
liver fibrosis, hepatocytes size, and binucleation. This improvement was due to the Fer-1-induced
attenuation of ferroptotic events in the liver of diabetic mice, such as accumulation of pro-oxidative
parameters (iron, lipofuscin, 4-HNE), decrease in expression level/activity of antioxidative defenserelated
molecules (GPX4, Nrf2, xCT, GSH, GCL, HO-1, SOD), and HMGB1 translocation from nucleus
into cytosol. We concluded that ferroptosis contributes to diabetes-related pathological changes in
the liver and that the targeting of ferroptosis represents a promising approach in the management of
diabetes-induced liver injury.
PB  - Basel: MDPI
T2  - International Journal of Molecular Sciences
T1  - Involvement of Ferroptosis in Diabetes-Induced Liver Pathology
IS  - 16
VL  - 23
DO  - 10.3390/ijms23169309
SP  - 9309
ER  - 

@article{
author = "Stančić, Ana and Veličković, Ksenija and Markelić, Milica and Grigorov, Ilijana and Saksida, Tamara and Savić, Nevena and Vučetić, Milica and Martinović, Vesna and Ivanović, Anđelija and Otašević, Vesna",
year = "2022",
abstract = "Cell death plays an important role in diabetes-induced liver dysfunction. Ferroptosis is a
newly defined regulated cell death caused by iron-dependent lipid peroxidation. Our previous studies
have shown that high glucose and streptozotocin (STZ) cause  -cell death through ferroptosis and
that ferrostatin-1 (Fer-1), an inhibitor of ferroptosis, improves  -cell viability, islet morphology, and
function. This study was aimed to examine in vivo the involvement of ferroptosis in diabetes-related
pathological changes in the liver. For this purpose, male C57BL/6 mice, in which diabetes was induced
with STZ (40 mg/kg/5 consecutive days), were treated with Fer-1 (1 mg/kg, from day 1–21 day). It
was found that in diabetic mice Fer-1 improved serum levels of ALT and triglycerides and decreased
liver fibrosis, hepatocytes size, and binucleation. This improvement was due to the Fer-1-induced
attenuation of ferroptotic events in the liver of diabetic mice, such as accumulation of pro-oxidative
parameters (iron, lipofuscin, 4-HNE), decrease in expression level/activity of antioxidative defenserelated
molecules (GPX4, Nrf2, xCT, GSH, GCL, HO-1, SOD), and HMGB1 translocation from nucleus
into cytosol. We concluded that ferroptosis contributes to diabetes-related pathological changes in
the liver and that the targeting of ferroptosis represents a promising approach in the management of
diabetes-induced liver injury.",
publisher = "Basel: MDPI",
journal = "International Journal of Molecular Sciences",
title = "Involvement of Ferroptosis in Diabetes-Induced Liver Pathology",
number = "16",
volume = "23",
doi = "10.3390/ijms23169309",
pages = "9309"
}

Stančić, A., Veličković, K., Markelić, M., Grigorov, I., Saksida, T., Savić, N., Vučetić, M., Martinović, V., Ivanović, A.,& Otašević, V.. (2022). Involvement of Ferroptosis in Diabetes-Induced Liver Pathology. in International Journal of Molecular Sciences
Basel: MDPI., 23(16), 9309.
https://doi.org/10.3390/ijms23169309

Stančić A, Veličković K, Markelić M, Grigorov I, Saksida T, Savić N, Vučetić M, Martinović V, Ivanović A, Otašević V. Involvement of Ferroptosis in Diabetes-Induced Liver Pathology. in International Journal of Molecular Sciences. 2022;23(16):9309.
doi:10.3390/ijms23169309 .

Stančić, Ana, Veličković, Ksenija, Markelić, Milica, Grigorov, Ilijana, Saksida, Tamara, Savić, Nevena, Vučetić, Milica, Martinović, Vesna, Ivanović, Anđelija, Otašević, Vesna, "Involvement of Ferroptosis in Diabetes-Induced Liver Pathology" in International Journal of Molecular Sciences, 23, no. 16 (2022):9309,
https://doi.org/10.3390/ijms23169309 . .

TY  - CONF
AU  - Stančić, Ana
AU  - Veličković, Ksenija
AU  - Markelić, Milica
AU  - Grigorov, Ilijana
AU  - Martinović, Vesna
AU  - Otašević, Vesna
PY  - 2022
UR  - https://meetings.embo.org/event/22-thiol-oxidation
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5264
AB  - Diabetes is considered as an important cause of wide spectrum of liver disorders with the significant implication of oxidative stress. Cell death assumes a central role in the etiology of most of the liver pathologies. We aim to describe here the ferroptotic phenotype in diabetic liver. For that purpose, male C57BL/6 mice were divided into three groups: diabetic (streptozotocin-treated, 40 mg/kg in 5 consecutive days), diabetic treated with ferrostatin-1 (Fer-1, 1 mg/kg, from day 1-21) and vehicle-treated (control) animals. Diabetes induced biochemical/morphological alterations in the liver, including increases in ALT and TGC levels as well as fibrosis, hepatocytes volume and number of binuclear cells. These were accompanied by following changes at the molecular level: i) increase in accumulation of prooxidative (such as iron, lipofuscin and 4-HNE) and proinflammatory (HMGB1) parameters and ii) decrease in antioxidative-related (Nrf2, xCT, GPX4, GCL, HO-1) parameters. All of these ferroptosis-related events in the liver of diabetic animals were diminished with Fer-1 treatment. Our study reveals ferroptotic phenotype as an important part of the diabetes-related pathological changes in the liver. Also, the results suggest that targeting of ferroptosis represents promising approach in the prevention and treatment of liver diseases accompanying diabetes.
PB  - Heidelberg: European Molecular Biology Organization (EMBO)
C3  - EMBO workshop: Thiol oxidation in biology: Biochemical mechanisms to physiological outcome; 2022 Oct 8-13; Sant Feliu de Guixols, Spain
T1  - Characterization of ferroptosis in diabetic liver
SP  - 51
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5264
ER  - 

@conference{
author = "Stančić, Ana and Veličković, Ksenija and Markelić, Milica and Grigorov, Ilijana and Martinović, Vesna and Otašević, Vesna",
year = "2022",
abstract = "Diabetes is considered as an important cause of wide spectrum of liver disorders with the significant implication of oxidative stress. Cell death assumes a central role in the etiology of most of the liver pathologies. We aim to describe here the ferroptotic phenotype in diabetic liver. For that purpose, male C57BL/6 mice were divided into three groups: diabetic (streptozotocin-treated, 40 mg/kg in 5 consecutive days), diabetic treated with ferrostatin-1 (Fer-1, 1 mg/kg, from day 1-21) and vehicle-treated (control) animals. Diabetes induced biochemical/morphological alterations in the liver, including increases in ALT and TGC levels as well as fibrosis, hepatocytes volume and number of binuclear cells. These were accompanied by following changes at the molecular level: i) increase in accumulation of prooxidative (such as iron, lipofuscin and 4-HNE) and proinflammatory (HMGB1) parameters and ii) decrease in antioxidative-related (Nrf2, xCT, GPX4, GCL, HO-1) parameters. All of these ferroptosis-related events in the liver of diabetic animals were diminished with Fer-1 treatment. Our study reveals ferroptotic phenotype as an important part of the diabetes-related pathological changes in the liver. Also, the results suggest that targeting of ferroptosis represents promising approach in the prevention and treatment of liver diseases accompanying diabetes.",
publisher = "Heidelberg: European Molecular Biology Organization (EMBO)",
journal = "EMBO workshop: Thiol oxidation in biology: Biochemical mechanisms to physiological outcome; 2022 Oct 8-13; Sant Feliu de Guixols, Spain",
title = "Characterization of ferroptosis in diabetic liver",
pages = "51",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5264"
}

Stančić, A., Veličković, K., Markelić, M., Grigorov, I., Martinović, V.,& Otašević, V.. (2022). Characterization of ferroptosis in diabetic liver. in EMBO workshop: Thiol oxidation in biology: Biochemical mechanisms to physiological outcome; 2022 Oct 8-13; Sant Feliu de Guixols, Spain
Heidelberg: European Molecular Biology Organization (EMBO)., 51.
https://hdl.handle.net/21.15107/rcub_ibiss_5264

Stančić A, Veličković K, Markelić M, Grigorov I, Martinović V, Otašević V. Characterization of ferroptosis in diabetic liver. in EMBO workshop: Thiol oxidation in biology: Biochemical mechanisms to physiological outcome; 2022 Oct 8-13; Sant Feliu de Guixols, Spain. 2022;:51.
https://hdl.handle.net/21.15107/rcub_ibiss_5264 .

Stančić, Ana, Veličković, Ksenija, Markelić, Milica, Grigorov, Ilijana, Martinović, Vesna, Otašević, Vesna, "Characterization of ferroptosis in diabetic liver" in EMBO workshop: Thiol oxidation in biology: Biochemical mechanisms to physiological outcome; 2022 Oct 8-13; Sant Feliu de Guixols, Spain (2022):51,
https://hdl.handle.net/21.15107/rcub_ibiss_5264 .

TY  - CONF
AU  - Ivanović, Anđelija
AU  - Martinović, Vesna
AU  - Stančić, Ana
AU  - Otašević, Vesna
AU  - Savić, Nevena
AU  - Đurašević, Siniša
AU  - Grigorov, Ilijana
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5194
AB  - Повећан унос хранљивих материја са високим садржајем енергије сматра се новим еволутивним изазовом. Иако се ћелијски и молекуларни ефекти хранљивих материја интензивно испитују, недовољно је сазнања која се тичу утицаја прекомерно унетих шећера на активност молекула укључених у регулаторне процесе.1,2 Међу недовољно испитаним деловањем је молекуларни аспект укључивања глукозе у одржавање редокс равнотеже у ћелијама, са аспекта деловања редокс осетљивих регулаторних протеина активираних посредством АТP-а. Стога је циљ ове студије био да се у јетри пацова старости 3(3М), 8(8М) и 16(16М) месеци испитају старосно-зависни ефекти осмонедељне исхране са 20% и 60% раствором декстрозе на експресију и активност редокс-сензитивног фактора транскрипције Nrf2 одговорног за иницирање антиоксидативног одговора (АОО) преко модулације експресије/активности антиоксидативних ензима глутатион пероксидазе (GPx), хем-оксигеназе (HO1), каталазе (CAT) и глутатион С-трансферазе (GST). Повећање количине унете глукозе довело је до повећања нивоа ATP-a у јетри 3М и 8М пацова и смањења увећаног ATP нивоа код 16М. Сразмерно унетој количини глукозе, нивоу ATP-a, eкспресији GLUT2 и ATP-зависног P2X7 рецептора, сваку старосну групу карактерише селективна модулација активности GPx, CAT и GST, активација Nrf2 и експресија HO-1 и CAT. Резултати указују на специфичности коришћеног Wistar Hannover соја у старосно-зависном АОО и на активну улогу Nrf2 у адаптацији на глукозом измењен оксидативни статус у јетри.
AB  - Povećan unos hranljivih materija sa visokim sadržajem energije smatra se novim evolutivnim izazovom. Iako se ćelijski i molekularni efekti hranljivih materija intenzivno ispituju, nedovoljno je saznanja koja se tiču uticaja prekomerno unetih šećera na aktivnost molekula uključenih u regulatorne procese.1,2 Među nedovoljno ispitanim delovanjem je molekularni aspekt uključivanja glukoze u održavanje redoks ravnoteže u ćelijama, sa aspekta delovanja redoks osetljivih regulatornih proteina aktiviranih posredstvom ATP-a. Stoga je cilj ove studije bio da se u jetri pacova starosti 3(3M), 8(8M) i 16(16M) meseci ispitaju starosno-zavisni efekti osmonedeljne ishrane sa 20% i 60% rastvorom dekstroze na ekspresiju i aktivnost redoks-senzitivnog faktora transkripcije Nrf2 odgovornog za iniciranje antioksidativnog odgovora (AOO) preko modulacije ekspresije/aktivnosti antioksidativnih enzima glutation peroksidaze (GPx), hem-oksigenaze (HO1), katalaze (CAT) i glutation S-transferaze (GST). Povećanje količine unete glukoze dovelo je do povećanja nivoa ATP-a u jetri 3M i 8M pacova i smanjenja uvećanog ATP nivoa kod 16M. Srazmerno unetoj količini glukoze, nivou ATP-a, ekspresiji GLUT2 i ATP-zavisnog P2X7 receptora, svaku starosnu grupu karakteriše selektivna modulacija aktivnosti GPx, CAT i GST, aktivacija Nrf2 i ekspresija HO-1 i CAT. Rezultati ukazuju na specifičnosti korišćenog Wistar Hannover soja u starosno-zavisnom AOO i na aktivnu ulogu Nrf2 u adaptaciji na glukozom izmenjen oksidativni status u jetri.
PB  - Belgrade: Serbian Biological Society
C3  - Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
T1  - Утицај повећаног уноса глукозе на молекуларнe механизмe редокс-регулације у јетри пацова различите старосне доби
T1  - Uticaj povećanog unosa glukoze na molekularne mehanizme redoks-regulacije u jetri pacova različite starosne dobi
VL  - пп 297
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5194
ER  - 

@conference{
author = "Ivanović, Anđelija and Martinović, Vesna and Stančić, Ana and Otašević, Vesna and Savić, Nevena and Đurašević, Siniša and Grigorov, Ilijana",
year = "2022",
abstract = "Повећан унос хранљивих материја са високим садржајем енергије сматра се новим еволутивним изазовом. Иако се ћелијски и молекуларни ефекти хранљивих материја интензивно испитују, недовољно је сазнања која се тичу утицаја прекомерно унетих шећера на активност молекула укључених у регулаторне процесе.1,2 Међу недовољно испитаним деловањем је молекуларни аспект укључивања глукозе у одржавање редокс равнотеже у ћелијама, са аспекта деловања редокс осетљивих регулаторних протеина активираних посредством АТP-а. Стога је циљ ове студије био да се у јетри пацова старости 3(3М), 8(8М) и 16(16М) месеци испитају старосно-зависни ефекти осмонедељне исхране са 20% и 60% раствором декстрозе на експресију и активност редокс-сензитивног фактора транскрипције Nrf2 одговорног за иницирање антиоксидативног одговора (АОО) преко модулације експресије/активности антиоксидативних ензима глутатион пероксидазе (GPx), хем-оксигеназе (HO1), каталазе (CAT) и глутатион С-трансферазе (GST). Повећање количине унете глукозе довело је до повећања нивоа ATP-a у јетри 3М и 8М пацова и смањења увећаног ATP нивоа код 16М. Сразмерно унетој количини глукозе, нивоу ATP-a, eкспресији GLUT2 и ATP-зависног P2X7 рецептора, сваку старосну групу карактерише селективна модулација активности GPx, CAT и GST, активација Nrf2 и експресија HO-1 и CAT. Резултати указују на специфичности коришћеног Wistar Hannover соја у старосно-зависном АОО и на активну улогу Nrf2 у адаптацији на глукозом измењен оксидативни статус у јетри., Povećan unos hranljivih materija sa visokim sadržajem energije smatra se novim evolutivnim izazovom. Iako se ćelijski i molekularni efekti hranljivih materija intenzivno ispituju, nedovoljno je saznanja koja se tiču uticaja prekomerno unetih šećera na aktivnost molekula uključenih u regulatorne procese.1,2 Među nedovoljno ispitanim delovanjem je molekularni aspekt uključivanja glukoze u održavanje redoks ravnoteže u ćelijama, sa aspekta delovanja redoks osetljivih regulatornih proteina aktiviranih posredstvom ATP-a. Stoga je cilj ove studije bio da se u jetri pacova starosti 3(3M), 8(8M) i 16(16M) meseci ispitaju starosno-zavisni efekti osmonedeljne ishrane sa 20% i 60% rastvorom dekstroze na ekspresiju i aktivnost redoks-senzitivnog faktora transkripcije Nrf2 odgovornog za iniciranje antioksidativnog odgovora (AOO) preko modulacije ekspresije/aktivnosti antioksidativnih enzima glutation peroksidaze (GPx), hem-oksigenaze (HO1), katalaze (CAT) i glutation S-transferaze (GST). Povećanje količine unete glukoze dovelo je do povećanja nivoa ATP-a u jetri 3M i 8M pacova i smanjenja uvećanog ATP nivoa kod 16M. Srazmerno unetoj količini glukoze, nivou ATP-a, ekspresiji GLUT2 i ATP-zavisnog P2X7 receptora, svaku starosnu grupu karakteriše selektivna modulacija aktivnosti GPx, CAT i GST, aktivacija Nrf2 i ekspresija HO-1 i CAT. Rezultati ukazuju na specifičnosti korišćenog Wistar Hannover soja u starosno-zavisnom AOO i na aktivnu ulogu Nrf2 u adaptaciji na glukozom izmenjen oksidativni status u jetri.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia",
title = "Утицај повећаног уноса глукозе на молекуларнe механизмe редокс-регулације у јетри пацова различите старосне доби, Uticaj povećanog unosa glukoze na molekularne mehanizme redoks-regulacije u jetri pacova različite starosne dobi",
volume = "пп 297",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5194"
}

Ivanović, A., Martinović, V., Stančić, A., Otašević, V., Savić, N., Đurašević, S.,& Grigorov, I.. (2022). Утицај повећаног уноса глукозе на молекуларнe механизмe редокс-регулације у јетри пацова различите старосне доби. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
Belgrade: Serbian Biological Society., пп 297.
https://hdl.handle.net/21.15107/rcub_ibiss_5194

Ivanović A, Martinović V, Stančić A, Otašević V, Savić N, Đurašević S, Grigorov I. Утицај повећаног уноса глукозе на молекуларнe механизмe редокс-регулације у јетри пацова различите старосне доби. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia. 2022;пп 297.
https://hdl.handle.net/21.15107/rcub_ibiss_5194 .

Ivanović, Anđelija, Martinović, Vesna, Stančić, Ana, Otašević, Vesna, Savić, Nevena, Đurašević, Siniša, Grigorov, Ilijana, "Утицај повећаног уноса глукозе на молекуларнe механизмe редокс-регулације у јетри пацова различите старосне доби" in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia, пп 297 (2022),
https://hdl.handle.net/21.15107/rcub_ibiss_5194 .

TY  - JOUR
AU  - Otašević, Vesna
AU  - Vučetić, M.
AU  - Grigorov, Ilijana
AU  - Martinović, Vesna
AU  - Stančić, Ana
PY  - 2021
UR  - https://www.hindawi.com/journals/omcl/2021/5537330/
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4417
AB  - Ferroptosis is a recently described form of regulated cell death characterized by intracellular iron accumulation and severe lipid peroxidation due to an impaired cysteine-glutathione-glutathione peroxidase 4 antioxidant defence axis. One of the hallmarks of ferroptosis is a specific morphological phenotype characterized by extensive ultrastructural changes of mitochondria. Increasing evidence suggests that mitochondria play a significant role in the induction and execution of ferroptosis. The present review summarizes existing knowledge about the mitochondrial impact on ferroptosis in different pathological states, primarily cancer, cardiovascular diseases, and neurodegenerative diseases. Additionally, we highlight pathologies in which the ferroptosis/mitochondria relation remains to be investigated, where the process of ferroptosis has been confirmed (such as liver- and kidney-related pathologies) and those in which ferroptosis has not been studied yet, such as diabetes. We will bring attention to avenues that could be followed in future research, based on the use of mitochondria-targeted approaches as anti- and proferroptotic strategies and directed to the improvement of existing and the development of novel therapeutic strategies.
T2  - Oxidative Medicine and Cellular Longevity
T1  - Ferroptosis in Different Pathological Contexts Seen through the Eyes of Mitochondria
VL  - 2021
DO  - 10.1155/2021/5537330
SP  - 1
EP  - 16
ER  - 

@article{
author = "Otašević, Vesna and Vučetić, M. and Grigorov, Ilijana and Martinović, Vesna and Stančić, Ana",
year = "2021",
abstract = "Ferroptosis is a recently described form of regulated cell death characterized by intracellular iron accumulation and severe lipid peroxidation due to an impaired cysteine-glutathione-glutathione peroxidase 4 antioxidant defence axis. One of the hallmarks of ferroptosis is a specific morphological phenotype characterized by extensive ultrastructural changes of mitochondria. Increasing evidence suggests that mitochondria play a significant role in the induction and execution of ferroptosis. The present review summarizes existing knowledge about the mitochondrial impact on ferroptosis in different pathological states, primarily cancer, cardiovascular diseases, and neurodegenerative diseases. Additionally, we highlight pathologies in which the ferroptosis/mitochondria relation remains to be investigated, where the process of ferroptosis has been confirmed (such as liver- and kidney-related pathologies) and those in which ferroptosis has not been studied yet, such as diabetes. We will bring attention to avenues that could be followed in future research, based on the use of mitochondria-targeted approaches as anti- and proferroptotic strategies and directed to the improvement of existing and the development of novel therapeutic strategies.",
journal = "Oxidative Medicine and Cellular Longevity",
title = "Ferroptosis in Different Pathological Contexts Seen through the Eyes of Mitochondria",
volume = "2021",
doi = "10.1155/2021/5537330",
pages = "1-16"
}

Otašević, V., Vučetić, M., Grigorov, I., Martinović, V.,& Stančić, A.. (2021). Ferroptosis in Different Pathological Contexts Seen through the Eyes of Mitochondria. in Oxidative Medicine and Cellular Longevity, 2021, 1-16.
https://doi.org/10.1155/2021/5537330

Otašević V, Vučetić M, Grigorov I, Martinović V, Stančić A. Ferroptosis in Different Pathological Contexts Seen through the Eyes of Mitochondria. in Oxidative Medicine and Cellular Longevity. 2021;2021:1-16.
doi:10.1155/2021/5537330 .

Otašević, Vesna, Vučetić, M., Grigorov, Ilijana, Martinović, Vesna, Stančić, Ana, "Ferroptosis in Different Pathological Contexts Seen through the Eyes of Mitochondria" in Oxidative Medicine and Cellular Longevity, 2021 (2021):1-16,
https://doi.org/10.1155/2021/5537330 . .

TY  - CONF
AU  - Stančić, Ana
AU  - Saksida, Tamara
AU  - Markelić, Milica
AU  - Vučetić, Milica
AU  - Grigorov, Ilijana
AU  - Martinović, Vesna
AU  - Ivanović, Anđelija
AU  - Veličković, Ksenija
AU  - Otašević, Vesna
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4899
AB  - Diabetes is a complex metabolic disorder which incidence rises in the epidemic fashion, suggesting the urgent need for new therapies. Its main pathological hallmark is loss of functional β-cells, and to date, several types of β-cell death have been described – necrosis, apoptosis, and autophagy. However, the role of ferroptosis in reducing β-cell population in diabetes remains elusive. In this study we aimed to examine whether and how this type of cell death is implicated in regulation of β-cell destiny in diabetes. For that purpose, Rin-5F insulin-producing pancreatic cells were treated with diabetes-mimicking factors – high glucose (HG) and H2O2, as well with commonly used diabetogenic agent streptozotocin (STZ). Results showed that HG, H2O2 and STZ induce the death of Rin-5F cells along with the accumulation of reactive oxygen species, lipid peroxides and iron; inactivation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and decrease in glutathione peroxidase 4 expression. This is consistent with the effect of the treatment with RSL-3, a well-known inducer of ferroptosis. Ferrostatin-1, a ferroptosis inhibitor, diminished above-stated effects and rescued cells from death. Our data revealed that β-cells underwent ferroptotic cell death under diabetogenic conditions. Results also implicate HG and H2O2 as contributing factors to ferroptosis of β-cells and suggest the novel mechanism of STZ diabetogenic action. Furthermore, the results shed a new light on antidiabetic strategy based on Nrf2 activation, putting it into the anti-ferroptotic context. In close, targeting ferroptosis in diabetes might be a new promising therapeutic approach based on preservation of β-cell population.
PB  - Belgrade: Faculty of Chemistry: Serbian Biochemical Society
C3  - Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia
T1  - Ferroptosis as a novel determinant of β-cell death in diabetic conditions
SP  - 146
EP  - 147
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4899
ER  - 

@conference{
author = "Stančić, Ana and Saksida, Tamara and Markelić, Milica and Vučetić, Milica and Grigorov, Ilijana and Martinović, Vesna and Ivanović, Anđelija and Veličković, Ksenija and Otašević, Vesna",
year = "2021",
abstract = "Diabetes is a complex metabolic disorder which incidence rises in the epidemic fashion, suggesting the urgent need for new therapies. Its main pathological hallmark is loss of functional β-cells, and to date, several types of β-cell death have been described – necrosis, apoptosis, and autophagy. However, the role of ferroptosis in reducing β-cell population in diabetes remains elusive. In this study we aimed to examine whether and how this type of cell death is implicated in regulation of β-cell destiny in diabetes. For that purpose, Rin-5F insulin-producing pancreatic cells were treated with diabetes-mimicking factors – high glucose (HG) and H2O2, as well with commonly used diabetogenic agent streptozotocin (STZ). Results showed that HG, H2O2 and STZ induce the death of Rin-5F cells along with the accumulation of reactive oxygen species, lipid peroxides and iron; inactivation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and decrease in glutathione peroxidase 4 expression. This is consistent with the effect of the treatment with RSL-3, a well-known inducer of ferroptosis. Ferrostatin-1, a ferroptosis inhibitor, diminished above-stated effects and rescued cells from death. Our data revealed that β-cells underwent ferroptotic cell death under diabetogenic conditions. Results also implicate HG and H2O2 as contributing factors to ferroptosis of β-cells and suggest the novel mechanism of STZ diabetogenic action. Furthermore, the results shed a new light on antidiabetic strategy based on Nrf2 activation, putting it into the anti-ferroptotic context. In close, targeting ferroptosis in diabetes might be a new promising therapeutic approach based on preservation of β-cell population.",
publisher = "Belgrade: Faculty of Chemistry: Serbian Biochemical Society",
journal = "Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia",
title = "Ferroptosis as a novel determinant of β-cell death in diabetic conditions",
pages = "146-147",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4899"
}

Stančić, A., Saksida, T., Markelić, M., Vučetić, M., Grigorov, I., Martinović, V., Ivanović, A., Veličković, K.,& Otašević, V.. (2021). Ferroptosis as a novel determinant of β-cell death in diabetic conditions. in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia
Belgrade: Faculty of Chemistry: Serbian Biochemical Society., 146-147.
https://hdl.handle.net/21.15107/rcub_ibiss_4899

Stančić A, Saksida T, Markelić M, Vučetić M, Grigorov I, Martinović V, Ivanović A, Veličković K, Otašević V. Ferroptosis as a novel determinant of β-cell death in diabetic conditions. in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia. 2021;:146-147.
https://hdl.handle.net/21.15107/rcub_ibiss_4899 .

Stančić, Ana, Saksida, Tamara, Markelić, Milica, Vučetić, Milica, Grigorov, Ilijana, Martinović, Vesna, Ivanović, Anđelija, Veličković, Ksenija, Otašević, Vesna, "Ferroptosis as a novel determinant of β-cell death in diabetic conditions" in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia (2021):146-147,
https://hdl.handle.net/21.15107/rcub_ibiss_4899 .

TY  - CONF
AU  - Markelić, Milica
AU  - Stančić, Ana
AU  - Saksida, Tamara
AU  - Vučetić, Milica
AU  - Grigorov, Ilijana
AU  - Martinović, Vesna
AU  - Veličković, Ksenija
AU  - Otašević, Vesna
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4897
AB  - Feroptosis is a recently described, programmed form of cell death. It is iron-dependant and characterized by the accumulation of lipid peroxides and reactive species. The main pathological hallmark of diabetes is -cell loss, and so far, several types of -cell death have been described. However, involvement of ferroptosis in -cell loss induced by diabetogenic factors is still unexplored.
The aim of this study was to investigate potential involvement of ferroptosis in the regulation of -cell loss in diabetes.For that purpose Rin-5F pancreatic -cells were treated with well-known diabetes-mimicking agents: high glucose (HG; 25 mM), hydrogen peroxide (H2O2; 75 μM) and streptozotocin (STZ; 10 mM) ) for 12h in the absence or presence of ferrostosis inhibitor, ferrostatin-1 (Fer-1, 1.5 μM). As a positive control, an inducer of ferroptosis RSL3 (3 μM) was used. Cells were prepared for flow citometry (death cell assay propidium iodide (PI) staining; dihydrorhodamine 123 (DHR) reactive oxygen species (ROS) detection) and microscopic analyses (phase contrast analysis of cells viability, morphology and cell confluence; Sudan III detection of neutral lipids and lipofuscin; Prussian blue detection of intracellular iron accumulation; C11-BODIPY detection of lipid peroxides and immunofluorescence detection of phospho-NFE2-related factor 2 (pNrf2)).Our results demonstrated that mimicking diabetic microenvironment by HG, STZ and H2O2 induced ferroptosis of -cells in vitro (Fig. 1), since observed alterations were similar to those induced by RSL3. As we observed microscopically, total cell number decreased, percentage of dead PI+ cells increased and cell changed their morphology from typical to spherical and detached. In addition, increased accumulation of lipid peroxides, ROS, lipids and/or lipofuscin and iron were observed after these treatments. Fer-1 rescued cells from death after all treatments, along with abolishing the effects of those treatments on ROS, lipid peroxides and iron content. Further, Fer-1-induced activation of Nrf2, which is well known as an antioxidant transcriptional factor that regulates level of many of the ferroptosis-related molecules including those involved in metabolism of GSH, iron and lipids. Taken together, our results demonstrated ferroptosis involvement in the -cell loss under diabetogenic conditions, thus proposing it as a new potential target in the diabetes therapy approach.
C3  - MC 2021 goes digital Microscopy Conference Proceedings; 2021 Aug 22-26; Online
T1  - Microscopic study of ferroptotic death of β-cells in diabetogenic conditions in vitro
SP  - 641
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4897
ER  - 

@conference{
author = "Markelić, Milica and Stančić, Ana and Saksida, Tamara and Vučetić, Milica and Grigorov, Ilijana and Martinović, Vesna and Veličković, Ksenija and Otašević, Vesna",
year = "2021",
abstract = "Feroptosis is a recently described, programmed form of cell death. It is iron-dependant and characterized by the accumulation of lipid peroxides and reactive species. The main pathological hallmark of diabetes is -cell loss, and so far, several types of -cell death have been described. However, involvement of ferroptosis in -cell loss induced by diabetogenic factors is still unexplored.
The aim of this study was to investigate potential involvement of ferroptosis in the regulation of -cell loss in diabetes.For that purpose Rin-5F pancreatic -cells were treated with well-known diabetes-mimicking agents: high glucose (HG; 25 mM), hydrogen peroxide (H2O2; 75 μM) and streptozotocin (STZ; 10 mM) ) for 12h in the absence or presence of ferrostosis inhibitor, ferrostatin-1 (Fer-1, 1.5 μM). As a positive control, an inducer of ferroptosis RSL3 (3 μM) was used. Cells were prepared for flow citometry (death cell assay propidium iodide (PI) staining; dihydrorhodamine 123 (DHR) reactive oxygen species (ROS) detection) and microscopic analyses (phase contrast analysis of cells viability, morphology and cell confluence; Sudan III detection of neutral lipids and lipofuscin; Prussian blue detection of intracellular iron accumulation; C11-BODIPY detection of lipid peroxides and immunofluorescence detection of phospho-NFE2-related factor 2 (pNrf2)).Our results demonstrated that mimicking diabetic microenvironment by HG, STZ and H2O2 induced ferroptosis of -cells in vitro (Fig. 1), since observed alterations were similar to those induced by RSL3. As we observed microscopically, total cell number decreased, percentage of dead PI+ cells increased and cell changed their morphology from typical to spherical and detached. In addition, increased accumulation of lipid peroxides, ROS, lipids and/or lipofuscin and iron were observed after these treatments. Fer-1 rescued cells from death after all treatments, along with abolishing the effects of those treatments on ROS, lipid peroxides and iron content. Further, Fer-1-induced activation of Nrf2, which is well known as an antioxidant transcriptional factor that regulates level of many of the ferroptosis-related molecules including those involved in metabolism of GSH, iron and lipids. Taken together, our results demonstrated ferroptosis involvement in the -cell loss under diabetogenic conditions, thus proposing it as a new potential target in the diabetes therapy approach.",
journal = "MC 2021 goes digital Microscopy Conference Proceedings; 2021 Aug 22-26; Online",
title = "Microscopic study of ferroptotic death of β-cells in diabetogenic conditions in vitro",
pages = "641",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4897"
}

Markelić, M., Stančić, A., Saksida, T., Vučetić, M., Grigorov, I., Martinović, V., Veličković, K.,& Otašević, V.. (2021). Microscopic study of ferroptotic death of β-cells in diabetogenic conditions in vitro. in MC 2021 goes digital Microscopy Conference Proceedings; 2021 Aug 22-26; Online, 641.
https://hdl.handle.net/21.15107/rcub_ibiss_4897

Markelić M, Stančić A, Saksida T, Vučetić M, Grigorov I, Martinović V, Veličković K, Otašević V. Microscopic study of ferroptotic death of β-cells in diabetogenic conditions in vitro. in MC 2021 goes digital Microscopy Conference Proceedings; 2021 Aug 22-26; Online. 2021;:641.
https://hdl.handle.net/21.15107/rcub_ibiss_4897 .

Markelić, Milica, Stančić, Ana, Saksida, Tamara, Vučetić, Milica, Grigorov, Ilijana, Martinović, Vesna, Veličković, Ksenija, Otašević, Vesna, "Microscopic study of ferroptotic death of β-cells in diabetogenic conditions in vitro" in MC 2021 goes digital Microscopy Conference Proceedings; 2021 Aug 22-26; Online (2021):641,
https://hdl.handle.net/21.15107/rcub_ibiss_4897 .

TY  - JOUR
AU  - Martinović, Vesna
AU  - Arambašić Jovanović, Jelena
AU  - Bogojević, Desanka
AU  - Ivanović, Anđelija
AU  - Otašević, Vesna
AU  - Stančić, Ana
AU  - Grigorov, Ilijana
PY  - 2020
UR  - http://www.doiserbia.nb.rs/Article.aspx?ID=0354-46642000049M
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4103
UR  - http://www.serbiosoc.org.rs/arch/index.php/abs/article/view/5980
AB  - Haptoglobin (Hp) is a hemoglobin-binding protein that prevents free hemoglobin-induced tissue oxidative damage. In streptozotocin-induced diabetic rats, the initial elevation of Hp expression in the serum and liver tends to decrease with diabetes progression, contributing to increased oxidative stress. Glucose toxicity and diabetic complications are closely related to increased modification of nucleocytoplasmic proteins by O-linked-N-acetylglucosamine (O-GlcNAc). We examined the contribution of O-GlcNAcylation of NF-κB p65 to changes in liver Hp expression in diabetic rats. WGA-affinity chromatography revealed a progressive increase in O-GlcNAcylation in nuclear NF-κB p65 during eight weeks of diabetes. DNA-affinity chromatography followed by immunoblot analysis revealed that decreased Hp expression at 4 and 8 weeks of diabetes was accompanied by the absence of Hp gene hormone-responsive element (HRE) occupancy with NF-κB p65, low occupancy with glucocorticoid receptor (GR), and almost no changes in STAT3 occupancy compared to 2 weeks, when Hp expression was highest. Coimmunoprecipitation experiments indicate that these events were the result of impaired NF-κB p65/STAT3 and GR/STAT3 interactions. Results suggest that the attenuation of Hp expression associated with diabetes was at least in part the result of O-GlcNAcylation of NF-κB p65, which prevents the formation of an effective transcription initiation complex on the Hp gene promoter.
PB  - Contribution of O-GlcNAc modification of NF-κB p65 in the attenuation of diabetes-induced haptoglobin expression in rat liver
T2  - Archives of Biological Sciences
T1  - Contribution of O-GlcNAc modification of NF-κB p65 in the attenuation of diabetes-induced haptoglobin expression in rat liver
IS  - 4
VL  - 72
DO  - 10.2298/ABS200928049M
SP  - 555
EP  - 565
ER  - 

@article{
author = "Martinović, Vesna and Arambašić Jovanović, Jelena and Bogojević, Desanka and Ivanović, Anđelija and Otašević, Vesna and Stančić, Ana and Grigorov, Ilijana",
year = "2020",
abstract = "Haptoglobin (Hp) is a hemoglobin-binding protein that prevents free hemoglobin-induced tissue oxidative damage. In streptozotocin-induced diabetic rats, the initial elevation of Hp expression in the serum and liver tends to decrease with diabetes progression, contributing to increased oxidative stress. Glucose toxicity and diabetic complications are closely related to increased modification of nucleocytoplasmic proteins by O-linked-N-acetylglucosamine (O-GlcNAc). We examined the contribution of O-GlcNAcylation of NF-κB p65 to changes in liver Hp expression in diabetic rats. WGA-affinity chromatography revealed a progressive increase in O-GlcNAcylation in nuclear NF-κB p65 during eight weeks of diabetes. DNA-affinity chromatography followed by immunoblot analysis revealed that decreased Hp expression at 4 and 8 weeks of diabetes was accompanied by the absence of Hp gene hormone-responsive element (HRE) occupancy with NF-κB p65, low occupancy with glucocorticoid receptor (GR), and almost no changes in STAT3 occupancy compared to 2 weeks, when Hp expression was highest. Coimmunoprecipitation experiments indicate that these events were the result of impaired NF-κB p65/STAT3 and GR/STAT3 interactions. Results suggest that the attenuation of Hp expression associated with diabetes was at least in part the result of O-GlcNAcylation of NF-κB p65, which prevents the formation of an effective transcription initiation complex on the Hp gene promoter.",
publisher = "Contribution of O-GlcNAc modification of NF-κB p65 in the attenuation of diabetes-induced haptoglobin expression in rat liver",
journal = "Archives of Biological Sciences",
title = "Contribution of O-GlcNAc modification of NF-κB p65 in the attenuation of diabetes-induced haptoglobin expression in rat liver",
number = "4",
volume = "72",
doi = "10.2298/ABS200928049M",
pages = "555-565"
}

Martinović, V., Arambašić Jovanović, J., Bogojević, D., Ivanović, A., Otašević, V., Stančić, A.,& Grigorov, I.. (2020). Contribution of O-GlcNAc modification of NF-κB p65 in the attenuation of diabetes-induced haptoglobin expression in rat liver. in Archives of Biological Sciences
Contribution of O-GlcNAc modification of NF-κB p65 in the attenuation of diabetes-induced haptoglobin expression in rat liver., 72(4), 555-565.
https://doi.org/10.2298/ABS200928049M

Martinović V, Arambašić Jovanović J, Bogojević D, Ivanović A, Otašević V, Stančić A, Grigorov I. Contribution of O-GlcNAc modification of NF-κB p65 in the attenuation of diabetes-induced haptoglobin expression in rat liver. in Archives of Biological Sciences. 2020;72(4):555-565.
doi:10.2298/ABS200928049M .

Martinović, Vesna, Arambašić Jovanović, Jelena, Bogojević, Desanka, Ivanović, Anđelija, Otašević, Vesna, Stančić, Ana, Grigorov, Ilijana, "Contribution of O-GlcNAc modification of NF-κB p65 in the attenuation of diabetes-induced haptoglobin expression in rat liver" in Archives of Biological Sciences, 72, no. 4 (2020):555-565,
https://doi.org/10.2298/ABS200928049M . .

TY  - JOUR
AU  - Đurašević, Siniša
AU  - Nikolić, Gorana
AU  - Todorović, Ana
AU  - Drakulić, Dunja
AU  - Pejić, Snežana
AU  - Martinović, Vesna
AU  - Mitić-Ćulafić, Dragana
AU  - Milić, Dragana
AU  - Kop, Tatjana J.
AU  - Jasnić, Nebojša
AU  - Đorđević, Jelena
AU  - Todorović, Zoran
PY  - 2020
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3645
AB  - The effects of twelve weeks of supplementation with fullerene C60 olive/coconut oil solution on a broad spectrum of parameters in rats were examined. The tissue bioaccumulation of C60 was shown to be tissue-specific, with the liver, heart, and adrenal glands being the organs of the greatest, and the kidney, brain, and spleen being the organs of the smallest accumulation. C60 did not change aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase serum activities level, nor the damage of liver cells DNA. There were no effects of fullerene on prooxidant-antioxidant balance in the liver, kidney, spleen, heart, and brain, nor any visible harmful effects on the liver, heart, aorta, spleen, kidney, and small intestine histology. Fullerene changed the gut microbiota structure towards the bacteria that ameliorate lipid homeostasis, causing a serum triglycerides concentration decrease. However, C60 significantly increased the insulin resistance, serum ascorbate oxidation, and brain malondialdehyde and advanced oxidation protein products level. The deteriorative effects of C60 on the brain and serum could be attributed to the specific physicochemical composition of these tissues, potentiating the C60 aggregation or biotransformation as the key element of its pro-oxidative action.
T2  - Food and Chemical Toxicology
T1  - Effects of fullerene C60 supplementation on gut microbiota and glucose and lipid homeostasis in rats
VL  - 140
DO  - 10.1016/j.fct.2020.111302
SP  - 111302
ER  - 

@article{
author = "Đurašević, Siniša and Nikolić, Gorana and Todorović, Ana and Drakulić, Dunja and Pejić, Snežana and Martinović, Vesna and Mitić-Ćulafić, Dragana and Milić, Dragana and Kop, Tatjana J. and Jasnić, Nebojša and Đorđević, Jelena and Todorović, Zoran",
year = "2020",
abstract = "The effects of twelve weeks of supplementation with fullerene C60 olive/coconut oil solution on a broad spectrum of parameters in rats were examined. The tissue bioaccumulation of C60 was shown to be tissue-specific, with the liver, heart, and adrenal glands being the organs of the greatest, and the kidney, brain, and spleen being the organs of the smallest accumulation. C60 did not change aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase serum activities level, nor the damage of liver cells DNA. There were no effects of fullerene on prooxidant-antioxidant balance in the liver, kidney, spleen, heart, and brain, nor any visible harmful effects on the liver, heart, aorta, spleen, kidney, and small intestine histology. Fullerene changed the gut microbiota structure towards the bacteria that ameliorate lipid homeostasis, causing a serum triglycerides concentration decrease. However, C60 significantly increased the insulin resistance, serum ascorbate oxidation, and brain malondialdehyde and advanced oxidation protein products level. The deteriorative effects of C60 on the brain and serum could be attributed to the specific physicochemical composition of these tissues, potentiating the C60 aggregation or biotransformation as the key element of its pro-oxidative action.",
journal = "Food and Chemical Toxicology",
title = "Effects of fullerene C60 supplementation on gut microbiota and glucose and lipid homeostasis in rats",
volume = "140",
doi = "10.1016/j.fct.2020.111302",
pages = "111302"
}

Đurašević, S., Nikolić, G., Todorović, A., Drakulić, D., Pejić, S., Martinović, V., Mitić-Ćulafić, D., Milić, D., Kop, T. J., Jasnić, N., Đorđević, J.,& Todorović, Z.. (2020). Effects of fullerene C60 supplementation on gut microbiota and glucose and lipid homeostasis in rats. in Food and Chemical Toxicology, 140, 111302.
https://doi.org/10.1016/j.fct.2020.111302

Đurašević S, Nikolić G, Todorović A, Drakulić D, Pejić S, Martinović V, Mitić-Ćulafić D, Milić D, Kop TJ, Jasnić N, Đorđević J, Todorović Z. Effects of fullerene C60 supplementation on gut microbiota and glucose and lipid homeostasis in rats. in Food and Chemical Toxicology. 2020;140:111302.
doi:10.1016/j.fct.2020.111302 .

Đurašević, Siniša, Nikolić, Gorana, Todorović, Ana, Drakulić, Dunja, Pejić, Snežana, Martinović, Vesna, Mitić-Ćulafić, Dragana, Milić, Dragana, Kop, Tatjana J., Jasnić, Nebojša, Đorđević, Jelena, Todorović, Zoran, "Effects of fullerene C60 supplementation on gut microbiota and glucose and lipid homeostasis in rats" in Food and Chemical Toxicology, 140 (2020):111302,
https://doi.org/10.1016/j.fct.2020.111302 . .

TY  - JOUR
AU  - Đurašević, Siniša
AU  - Jasnić, Nebojša
AU  - Prokić, Marko
AU  - Grigorov, Ilijana
AU  - Martinović, Vesna
AU  - Đorđević, Jelena
AU  - Pavlović, Slađan
PY  - 2019
UR  - http://xlink.rsc.org/?DOI=C9FO00107G
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3343
AB  - The aim of this study was to investigate the potential protective effect of virgin coconut oil (VCO) on oxidative stress parameters in the liver, kidneys and heart of alloxan-induced (150 mg kg-1 i.p.-1) diabetes in rats. Our results showed that daily supplementation of VCO (20% of food) for 16 weeks significantly (p < 0.05) ameliorates some deleterious effects caused by alloxan. VCO reduced the diabetes-related increase in food (82.15 ± 1.49 vs. 145.51 ± 4.81 g per kg b.m. per day) and water (305.49 ± 6.09 vs. 583.98 ± 14.80 mL per kg b.m. per day) intake, and the decrease in the body mass gain (0.56 ± 0.16 vs. -2.13 ± 0.49 g per 100 g b.m. per week). In all three tissues, diabetes caused an increase in the concentration of total glutathione and sulfhydryl groups, and catalase and glutathione S-transferase activities, without changes in superoxide dismutase activity. Glutathione peroxidase activity was increased in the kidneys and heart, but not in the liver of the diabetic animals, while glutathione reductase activity was increased in the liver and the kidneys, and not in the heart. The simultaneous VCO supplementation increased the concentration of the sulfhydryl group in all three tissues of diabetic animals and decreased the glutathione S-transferase activity and glutathione concentration, without affecting the glutathione reductase activity. In the liver of diabetic animals it decreased superoxide dismutase, catalase and glutathione peroxidase activities, in the heart catalase and glutathione peroxidase activities, and in the kidney catalase activity only. The results of canonical discriminant analysis of oxidative stress parameters revealed that VCO exerts its effects in a tissue-specific manner.
T2  - Food & Function
T1  - The protective role of virgin coconut oil on the alloxan-induced oxidative stress in the liver, kidneys and heart of diabetic rats.
IS  - 4
VL  - 10
DO  - 10.1039/c9fo00107g
SP  - 2114
EP  - 2124
ER  - 

@article{
author = "Đurašević, Siniša and Jasnić, Nebojša and Prokić, Marko and Grigorov, Ilijana and Martinović, Vesna and Đorđević, Jelena and Pavlović, Slađan",
year = "2019",
abstract = "The aim of this study was to investigate the potential protective effect of virgin coconut oil (VCO) on oxidative stress parameters in the liver, kidneys and heart of alloxan-induced (150 mg kg-1 i.p.-1) diabetes in rats. Our results showed that daily supplementation of VCO (20% of food) for 16 weeks significantly (p < 0.05) ameliorates some deleterious effects caused by alloxan. VCO reduced the diabetes-related increase in food (82.15 ± 1.49 vs. 145.51 ± 4.81 g per kg b.m. per day) and water (305.49 ± 6.09 vs. 583.98 ± 14.80 mL per kg b.m. per day) intake, and the decrease in the body mass gain (0.56 ± 0.16 vs. -2.13 ± 0.49 g per 100 g b.m. per week). In all three tissues, diabetes caused an increase in the concentration of total glutathione and sulfhydryl groups, and catalase and glutathione S-transferase activities, without changes in superoxide dismutase activity. Glutathione peroxidase activity was increased in the kidneys and heart, but not in the liver of the diabetic animals, while glutathione reductase activity was increased in the liver and the kidneys, and not in the heart. The simultaneous VCO supplementation increased the concentration of the sulfhydryl group in all three tissues of diabetic animals and decreased the glutathione S-transferase activity and glutathione concentration, without affecting the glutathione reductase activity. In the liver of diabetic animals it decreased superoxide dismutase, catalase and glutathione peroxidase activities, in the heart catalase and glutathione peroxidase activities, and in the kidney catalase activity only. The results of canonical discriminant analysis of oxidative stress parameters revealed that VCO exerts its effects in a tissue-specific manner.",
journal = "Food & Function",
title = "The protective role of virgin coconut oil on the alloxan-induced oxidative stress in the liver, kidneys and heart of diabetic rats.",
number = "4",
volume = "10",
doi = "10.1039/c9fo00107g",
pages = "2114-2124"
}

Đurašević, S., Jasnić, N., Prokić, M., Grigorov, I., Martinović, V., Đorđević, J.,& Pavlović, S.. (2019). The protective role of virgin coconut oil on the alloxan-induced oxidative stress in the liver, kidneys and heart of diabetic rats.. in Food & Function, 10(4), 2114-2124.
https://doi.org/10.1039/c9fo00107g

Đurašević S, Jasnić N, Prokić M, Grigorov I, Martinović V, Đorđević J, Pavlović S. The protective role of virgin coconut oil on the alloxan-induced oxidative stress in the liver, kidneys and heart of diabetic rats.. in Food & Function. 2019;10(4):2114-2124.
doi:10.1039/c9fo00107g .

Đurašević, Siniša, Jasnić, Nebojša, Prokić, Marko, Grigorov, Ilijana, Martinović, Vesna, Đorđević, Jelena, Pavlović, Slađan, "The protective role of virgin coconut oil on the alloxan-induced oxidative stress in the liver, kidneys and heart of diabetic rats." in Food & Function, 10, no. 4 (2019):2114-2124,
https://doi.org/10.1039/c9fo00107g . .

TY  - JOUR
AU  - Đurašević, Siniša
AU  - Jasnić, Nebojša
AU  - Prokić, Marko
AU  - Grigorov, Ilijana
AU  - Martinović, Vesna
AU  - Đorđević, Jelena
AU  - Pavlović, Slađan
PY  - 2019
UR  - http://xlink.rsc.org/?DOI=C9FO00107G
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3341
AB  - The aim of this study was to investigate the potential protective effect of virgin coconut oil (VCO) on oxidative stress parameters in the liver, kidneys and heart of alloxan-induced (150 mg kg-1 i.p.-1) diabetes in rats. Our results showed that daily supplementation of VCO (20% of food) for 16 weeks significantly (p < 0.05) ameliorates some deleterious effects caused by alloxan. VCO reduced the diabetes-related increase in food (82.15 ± 1.49 vs. 145.51 ± 4.81 g per kg b.m. per day) and water (305.49 ± 6.09 vs. 583.98 ± 14.80 mL per kg b.m. per day) intake, and the decrease in the body mass gain (0.56 ± 0.16 vs. -2.13 ± 0.49 g per 100 g b.m. per week). In all three tissues, diabetes caused an increase in the concentration of total glutathione and sulfhydryl groups, and catalase and glutathione S-transferase activities, without changes in superoxide dismutase activity. Glutathione peroxidase activity was increased in the kidneys and heart, but not in the liver of the diabetic animals, while glutathione reductase activity was increased in the liver and the kidneys, and not in the heart. The simultaneous VCO supplementation increased the concentration of the sulfhydryl group in all three tissues of diabetic animals and decreased the glutathione S-transferase activity and glutathione concentration, without affecting the glutathione reductase activity. In the liver of diabetic animals it decreased superoxide dismutase, catalase and glutathione peroxidase activities, in the heart catalase and glutathione peroxidase activities, and in the kidney catalase activity only. The results of canonical discriminant analysis of oxidative stress parameters revealed that VCO exerts its effects in a tissue-specific manner.
T2  - Food & Function
T1  - The protective role of virgin coconut oil on the alloxan-induced oxidative stress in the liver, kidneys and heart of diabetic rats.
IS  - 4
VL  - 10
DO  - 10.1039/c9fo00107g
SP  - 2114
EP  - 2124
ER  - 

@article{
author = "Đurašević, Siniša and Jasnić, Nebojša and Prokić, Marko and Grigorov, Ilijana and Martinović, Vesna and Đorđević, Jelena and Pavlović, Slađan",
year = "2019",
abstract = "The aim of this study was to investigate the potential protective effect of virgin coconut oil (VCO) on oxidative stress parameters in the liver, kidneys and heart of alloxan-induced (150 mg kg-1 i.p.-1) diabetes in rats. Our results showed that daily supplementation of VCO (20% of food) for 16 weeks significantly (p < 0.05) ameliorates some deleterious effects caused by alloxan. VCO reduced the diabetes-related increase in food (82.15 ± 1.49 vs. 145.51 ± 4.81 g per kg b.m. per day) and water (305.49 ± 6.09 vs. 583.98 ± 14.80 mL per kg b.m. per day) intake, and the decrease in the body mass gain (0.56 ± 0.16 vs. -2.13 ± 0.49 g per 100 g b.m. per week). In all three tissues, diabetes caused an increase in the concentration of total glutathione and sulfhydryl groups, and catalase and glutathione S-transferase activities, without changes in superoxide dismutase activity. Glutathione peroxidase activity was increased in the kidneys and heart, but not in the liver of the diabetic animals, while glutathione reductase activity was increased in the liver and the kidneys, and not in the heart. The simultaneous VCO supplementation increased the concentration of the sulfhydryl group in all three tissues of diabetic animals and decreased the glutathione S-transferase activity and glutathione concentration, without affecting the glutathione reductase activity. In the liver of diabetic animals it decreased superoxide dismutase, catalase and glutathione peroxidase activities, in the heart catalase and glutathione peroxidase activities, and in the kidney catalase activity only. The results of canonical discriminant analysis of oxidative stress parameters revealed that VCO exerts its effects in a tissue-specific manner.",
journal = "Food & Function",
title = "The protective role of virgin coconut oil on the alloxan-induced oxidative stress in the liver, kidneys and heart of diabetic rats.",
number = "4",
volume = "10",
doi = "10.1039/c9fo00107g",
pages = "2114-2124"
}

Đurašević, S., Jasnić, N., Prokić, M., Grigorov, I., Martinović, V., Đorđević, J.,& Pavlović, S.. (2019). The protective role of virgin coconut oil on the alloxan-induced oxidative stress in the liver, kidneys and heart of diabetic rats.. in Food & Function, 10(4), 2114-2124.
https://doi.org/10.1039/c9fo00107g

Đurašević S, Jasnić N, Prokić M, Grigorov I, Martinović V, Đorđević J, Pavlović S. The protective role of virgin coconut oil on the alloxan-induced oxidative stress in the liver, kidneys and heart of diabetic rats.. in Food & Function. 2019;10(4):2114-2124.
doi:10.1039/c9fo00107g .

Đurašević, Siniša, Jasnić, Nebojša, Prokić, Marko, Grigorov, Ilijana, Martinović, Vesna, Đorđević, Jelena, Pavlović, Slađan, "The protective role of virgin coconut oil on the alloxan-induced oxidative stress in the liver, kidneys and heart of diabetic rats." in Food & Function, 10, no. 4 (2019):2114-2124,
https://doi.org/10.1039/c9fo00107g . .

TY  - CONF
AU  - Petrović, Anja
AU  - Bogojević, Desanka
AU  - Ivanović-Matić, Svetlana
AU  - Martinović, Vesna
AU  - Korać, Aleksandra
AU  - Jovanović-Stojanov, Sofija
AU  - Grigorov, Ilijana
PY  - 2018
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5660
AB  - Oxidative stress. cell damage and cell death underlies the etiology of liver damage/dysfunction  in  diabetes.  Bigh  Mobility  Group  Box 1 (HMGB1) is a nuclear protein that is  released  from damaged/stressed  liver cells during, diabetes and  contributes to oxidative  stresse-mediated autophagy  an cell death/survival. Since ethyl pyruvate (EP) an HMGB1 relase/expession and autophagy in the liver of diabetic rats. Diabetes was indused by streptozotocin(65mg/kg). Pretreated group of diabetes rats- (EP+D) startedl treatment  with EP (80mg/kg/daily) three·days before
diabetes induction,  while  in  the  second  group  (D+EP}  treatment  start   ten  days after diabetes induuction. In compcarison with D+EP group, EP+D group had better glycemic  status  and  higher  activity  of  antioxidative enzyme  SOD  and CAT in diabetic  liver.  According  to  western  immunoblot   analyses,  EP+D  group   sliowed higher     expression     of     extracellular    HMGB l     in    comparison      with D+EP. Consequently  detected increase in HMGB1/RAGE interactions in EP+D group were followed  by higher expression of LC3-II, HMGB1/Beclin 1 interaction and activation  of  autophagy.  Expression  of  LC3-II  and   HMGB1/Beclin 1 interaction were  at  the  control  level  in  D+EP.  Preserved  liver   morphology  in  both  EP   treated groups, observed  by  electron  microscopy,   implicated  existence   of   adaptive mechanisms  in EP+D  group.  Further  analyses  showed that  protective autophagy (mitophagy) was enhanced in EP+D group compared with diabetic and D+EP groups. Thus treatment of  diabetic  patients  with  EP  may  constitute  a  new strategy for the treatment  of  diabetes related  tissue  injury.
PB  - Belgrade: Serbian Physiological Society
C3  - Abstract book: 4th Congress of Physiological Sciences of Serbia with International Participation: Current Trends in Physiological Sciences: from cell signals to the biology of aging; 2018 Sep 19-23; Niš, Serbia
T1  - Pretreatment of diabetic rats with ethyl piruvate upregulates HMGB-driven protective autophagy in the liver
SP  - 108
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5660
ER  - 

@conference{
author = "Petrović, Anja and Bogojević, Desanka and Ivanović-Matić, Svetlana and Martinović, Vesna and Korać, Aleksandra and Jovanović-Stojanov, Sofija and Grigorov, Ilijana",
year = "2018",
abstract = "Oxidative stress. cell damage and cell death underlies the etiology of liver damage/dysfunction  in  diabetes.  Bigh  Mobility  Group  Box 1 (HMGB1) is a nuclear protein that is  released  from damaged/stressed  liver cells during, diabetes and  contributes to oxidative  stresse-mediated autophagy  an cell death/survival. Since ethyl pyruvate (EP) an HMGB1 relase/expession and autophagy in the liver of diabetic rats. Diabetes was indused by streptozotocin(65mg/kg). Pretreated group of diabetes rats- (EP+D) startedl treatment  with EP (80mg/kg/daily) three·days before
diabetes induction,  while  in  the  second  group  (D+EP}  treatment  start   ten  days after diabetes induuction. In compcarison with D+EP group, EP+D group had better glycemic  status  and  higher  activity  of  antioxidative enzyme  SOD  and CAT in diabetic  liver.  According  to  western  immunoblot   analyses,  EP+D  group   sliowed higher     expression     of     extracellular    HMGB l     in    comparison      with D+EP. Consequently  detected increase in HMGB1/RAGE interactions in EP+D group were followed  by higher expression of LC3-II, HMGB1/Beclin 1 interaction and activation  of  autophagy.  Expression  of  LC3-II  and   HMGB1/Beclin 1 interaction were  at  the  control  level  in  D+EP.  Preserved  liver   morphology  in  both  EP   treated groups, observed  by  electron  microscopy,   implicated  existence   of   adaptive mechanisms  in EP+D  group.  Further  analyses  showed that  protective autophagy (mitophagy) was enhanced in EP+D group compared with diabetic and D+EP groups. Thus treatment of  diabetic  patients  with  EP  may  constitute  a  new strategy for the treatment  of  diabetes related  tissue  injury.",
publisher = "Belgrade: Serbian Physiological Society",
journal = "Abstract book: 4th Congress of Physiological Sciences of Serbia with International Participation: Current Trends in Physiological Sciences: from cell signals to the biology of aging; 2018 Sep 19-23; Niš, Serbia",
title = "Pretreatment of diabetic rats with ethyl piruvate upregulates HMGB-driven protective autophagy in the liver",
pages = "108",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5660"
}

Petrović, A., Bogojević, D., Ivanović-Matić, S., Martinović, V., Korać, A., Jovanović-Stojanov, S.,& Grigorov, I.. (2018). Pretreatment of diabetic rats with ethyl piruvate upregulates HMGB-driven protective autophagy in the liver. in Abstract book: 4th Congress of Physiological Sciences of Serbia with International Participation: Current Trends in Physiological Sciences: from cell signals to the biology of aging; 2018 Sep 19-23; Niš, Serbia
Belgrade: Serbian Physiological Society., 108.
https://hdl.handle.net/21.15107/rcub_ibiss_5660

Petrović A, Bogojević D, Ivanović-Matić S, Martinović V, Korać A, Jovanović-Stojanov S, Grigorov I. Pretreatment of diabetic rats with ethyl piruvate upregulates HMGB-driven protective autophagy in the liver. in Abstract book: 4th Congress of Physiological Sciences of Serbia with International Participation: Current Trends in Physiological Sciences: from cell signals to the biology of aging; 2018 Sep 19-23; Niš, Serbia. 2018;:108.
https://hdl.handle.net/21.15107/rcub_ibiss_5660 .

Petrović, Anja, Bogojević, Desanka, Ivanović-Matić, Svetlana, Martinović, Vesna, Korać, Aleksandra, Jovanović-Stojanov, Sofija, Grigorov, Ilijana, "Pretreatment of diabetic rats with ethyl piruvate upregulates HMGB-driven protective autophagy in the liver" in Abstract book: 4th Congress of Physiological Sciences of Serbia with International Participation: Current Trends in Physiological Sciences: from cell signals to the biology of aging; 2018 Sep 19-23; Niš, Serbia (2018):108,
https://hdl.handle.net/21.15107/rcub_ibiss_5660 .

TY  - CONF
AU  - Petrović, Anja
AU  - Bogojević, Desanka
AU  - Ivanović Matić, Svetlana
AU  - Martinović, Vesna
AU  - Korać, Aleksandra
AU  - Jovanović Stojanov, Sofija
AU  - Poznanović, Goran
AU  - Grigorov, Ilijana
PY  - 2018
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5237
AB  - Oxidative stress through changes in antioxidative enzyme activities, glutathione metabolism and lipid peroxidation, leads to cell damage and even cell death. These changes are integrated in the pathogenetic mechanisms of the long-term, specific complications of diabetes, such as neuropathy, retinopathy, cardiomyopathy, nephropathy and hepatopathy. Recent studies have shed light on new redox sensitive endogenous targets which are important regulators of oxidative stress-induced damage. HMGB1 is a nuclear chaperone with an inflammatory function when released in the extracellular space. Extracellular HMGB1, through interaction with TLR4 receptors in its oxidized state, and with RAGE in its reduced state, controls the equilibrium between apoptosis and autophagy. HMGB1 is  a redox sensitive protein with a potentially harmful role. We therefore analyzed the changes in HMGB1 regulated signaling pathways by immunoprecipitation and Western blot that can lead to cell death or cell survival in the liver of streptozotocin (STZ)-induced diabetic rats during decreased oxidative stress after melatonin administration, and when HMGB1 release was inhibited by ethyl pyruvate. Inhibition of HMGB1 release decreased both apoptosis and autophagy, and supported the unchanged state in liver cells in STZ-treated rats as compared to the control animals. The decrease in oxidative stress achieved with melatonin decreased HMGB1 driven apoptosis but upregulated HMGB1 regulated protective autophagy, mitophagy in particular as the second level of antioxidative defense which was detected by electron microscopy. It provided a selective advantage, minimizing oxidant insults when primary antioxidant activities are compromised during oxidative stress. This adaptation led to improved cell survival in the liver of STZ-treated rats. These results showed that modulation of the role of HMGB1 in the extracellular space that was achieved by a decrease in oxidative stress is more desirable than complete inhibition of its release because HMGB1 has a protective role against oxidative injuries in diabetic liver.
PB  - Belgrade: Serbian Society for Mitochondrial and Free Radical Physiology
C3  - Book of Abstracts: Fourth Congress Challenges in Redox Biology: SSMFRP-2018; 2018 Sep 28-30; Belgrade, Serbia
T1  - The level of oxidative stress determines the role of extracellular HMGB1 protein in diabetic liver
SP  - 43
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5237
ER  - 

@conference{
author = "Petrović, Anja and Bogojević, Desanka and Ivanović Matić, Svetlana and Martinović, Vesna and Korać, Aleksandra and Jovanović Stojanov, Sofija and Poznanović, Goran and Grigorov, Ilijana",
year = "2018",
abstract = "Oxidative stress through changes in antioxidative enzyme activities, glutathione metabolism and lipid peroxidation, leads to cell damage and even cell death. These changes are integrated in the pathogenetic mechanisms of the long-term, specific complications of diabetes, such as neuropathy, retinopathy, cardiomyopathy, nephropathy and hepatopathy. Recent studies have shed light on new redox sensitive endogenous targets which are important regulators of oxidative stress-induced damage. HMGB1 is a nuclear chaperone with an inflammatory function when released in the extracellular space. Extracellular HMGB1, through interaction with TLR4 receptors in its oxidized state, and with RAGE in its reduced state, controls the equilibrium between apoptosis and autophagy. HMGB1 is  a redox sensitive protein with a potentially harmful role. We therefore analyzed the changes in HMGB1 regulated signaling pathways by immunoprecipitation and Western blot that can lead to cell death or cell survival in the liver of streptozotocin (STZ)-induced diabetic rats during decreased oxidative stress after melatonin administration, and when HMGB1 release was inhibited by ethyl pyruvate. Inhibition of HMGB1 release decreased both apoptosis and autophagy, and supported the unchanged state in liver cells in STZ-treated rats as compared to the control animals. The decrease in oxidative stress achieved with melatonin decreased HMGB1 driven apoptosis but upregulated HMGB1 regulated protective autophagy, mitophagy in particular as the second level of antioxidative defense which was detected by electron microscopy. It provided a selective advantage, minimizing oxidant insults when primary antioxidant activities are compromised during oxidative stress. This adaptation led to improved cell survival in the liver of STZ-treated rats. These results showed that modulation of the role of HMGB1 in the extracellular space that was achieved by a decrease in oxidative stress is more desirable than complete inhibition of its release because HMGB1 has a protective role against oxidative injuries in diabetic liver.",
publisher = "Belgrade: Serbian Society for Mitochondrial and Free Radical Physiology",
journal = "Book of Abstracts: Fourth Congress Challenges in Redox Biology: SSMFRP-2018; 2018 Sep 28-30; Belgrade, Serbia",
title = "The level of oxidative stress determines the role of extracellular HMGB1 protein in diabetic liver",
pages = "43",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5237"
}

Petrović, A., Bogojević, D., Ivanović Matić, S., Martinović, V., Korać, A., Jovanović Stojanov, S., Poznanović, G.,& Grigorov, I.. (2018). The level of oxidative stress determines the role of extracellular HMGB1 protein in diabetic liver. in Book of Abstracts: Fourth Congress Challenges in Redox Biology: SSMFRP-2018; 2018 Sep 28-30; Belgrade, Serbia
Belgrade: Serbian Society for Mitochondrial and Free Radical Physiology., 43.
https://hdl.handle.net/21.15107/rcub_ibiss_5237

Petrović A, Bogojević D, Ivanović Matić S, Martinović V, Korać A, Jovanović Stojanov S, Poznanović G, Grigorov I. The level of oxidative stress determines the role of extracellular HMGB1 protein in diabetic liver. in Book of Abstracts: Fourth Congress Challenges in Redox Biology: SSMFRP-2018; 2018 Sep 28-30; Belgrade, Serbia. 2018;:43.
https://hdl.handle.net/21.15107/rcub_ibiss_5237 .

Petrović, Anja, Bogojević, Desanka, Ivanović Matić, Svetlana, Martinović, Vesna, Korać, Aleksandra, Jovanović Stojanov, Sofija, Poznanović, Goran, Grigorov, Ilijana, "The level of oxidative stress determines the role of extracellular HMGB1 protein in diabetic liver" in Book of Abstracts: Fourth Congress Challenges in Redox Biology: SSMFRP-2018; 2018 Sep 28-30; Belgrade, Serbia (2018):43,
https://hdl.handle.net/21.15107/rcub_ibiss_5237 .

TY  - JOUR
AU  - Jovanović Stojanov, Sofija
AU  - Martinović, Vesna
AU  - Bogojević, Desanka
AU  - Poznanović, Goran
AU  - Petrović, Anja
AU  - Ivanović Matić, Svetlana
AU  - Grigorov, Ilijana
PY  - 2018
UR  - http://link.springer.com/10.1007/s13105-018-0626-0
UR  - http://www.ncbi.nlm.nih.gov/pubmed/29611132
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3068
AB  - Chronic inflammation plays an essential role in the development of diabetic complications. Understanding the molecular mechanisms that support inflammation is a prerequisite for the design of novel anti-inflammatory therapies. These would take into consideration circulating levels of cytokines and damage-associated molecular patterns (DAMPs) that include the high mobility group box 1 (HMGB1) protein which, in part, promotes the inflammatory response through TLR4 signaling. The liver, as the source of circulating cytokines and acute-phase proteins, contributes to the control of systemic inflammation. We previously found that liver injury in streptozotocin-induced diabetic rats correlated with the level of oxidative stress, increased expression of HMGB1, and with the activation of TLR4-mediated cell death pathways. In the present work, we examined the effects of ethyl pyruvate (EP), an inhibitor of HMGB1 release/expression, on the modulation of activation of the HMGB1/TLR4 inflammatory cascade in diabetic liver. We observed that increased expression of inflammatory markers, TNF-α, IL-6, and haptoglobin in diabetic liver was associated with increased HMGB1/TLR4 interaction, activation of MAPK (p38, ERK, JNK)/NF-κB p65 and JAK1/STAT3 signaling pathways, and with decreased expression of Nrf2-regulated antioxidative enzymes. The reduction in HMGB1 expression as the result of EP administration reduced the pro-inflammatory activity of HMGB1 and exerted a protective effect on diabetic liver, which was observed as improved liver histology and antioxidant and inflammatory statuses. Our results suggest that prevention of HMGB1 release and blockage of the HMGB/TLR4 axis represents a potentially effective therapeutic strategy aimed at ameliorating diabetes-induced inflammation and ensuing liver injury.
T2  - Journal of Physiology and Biochemistry
T1  - Modulation of diabetes-related liver injury by the HMGB1/TLR4 inflammatory pathway.
IS  - 2
VL  - 74
DO  - 10.1007/s13105-018-0626-0
SP  - 345
EP  - 358
ER  - 

@article{
author = "Jovanović Stojanov, Sofija and Martinović, Vesna and Bogojević, Desanka and Poznanović, Goran and Petrović, Anja and Ivanović Matić, Svetlana and Grigorov, Ilijana",
year = "2018",
abstract = "Chronic inflammation plays an essential role in the development of diabetic complications. Understanding the molecular mechanisms that support inflammation is a prerequisite for the design of novel anti-inflammatory therapies. These would take into consideration circulating levels of cytokines and damage-associated molecular patterns (DAMPs) that include the high mobility group box 1 (HMGB1) protein which, in part, promotes the inflammatory response through TLR4 signaling. The liver, as the source of circulating cytokines and acute-phase proteins, contributes to the control of systemic inflammation. We previously found that liver injury in streptozotocin-induced diabetic rats correlated with the level of oxidative stress, increased expression of HMGB1, and with the activation of TLR4-mediated cell death pathways. In the present work, we examined the effects of ethyl pyruvate (EP), an inhibitor of HMGB1 release/expression, on the modulation of activation of the HMGB1/TLR4 inflammatory cascade in diabetic liver. We observed that increased expression of inflammatory markers, TNF-α, IL-6, and haptoglobin in diabetic liver was associated with increased HMGB1/TLR4 interaction, activation of MAPK (p38, ERK, JNK)/NF-κB p65 and JAK1/STAT3 signaling pathways, and with decreased expression of Nrf2-regulated antioxidative enzymes. The reduction in HMGB1 expression as the result of EP administration reduced the pro-inflammatory activity of HMGB1 and exerted a protective effect on diabetic liver, which was observed as improved liver histology and antioxidant and inflammatory statuses. Our results suggest that prevention of HMGB1 release and blockage of the HMGB/TLR4 axis represents a potentially effective therapeutic strategy aimed at ameliorating diabetes-induced inflammation and ensuing liver injury.",
journal = "Journal of Physiology and Biochemistry",
title = "Modulation of diabetes-related liver injury by the HMGB1/TLR4 inflammatory pathway.",
number = "2",
volume = "74",
doi = "10.1007/s13105-018-0626-0",
pages = "345-358"
}

Jovanović Stojanov, S., Martinović, V., Bogojević, D., Poznanović, G., Petrović, A., Ivanović Matić, S.,& Grigorov, I.. (2018). Modulation of diabetes-related liver injury by the HMGB1/TLR4 inflammatory pathway.. in Journal of Physiology and Biochemistry, 74(2), 345-358.
https://doi.org/10.1007/s13105-018-0626-0

Jovanović Stojanov S, Martinović V, Bogojević D, Poznanović G, Petrović A, Ivanović Matić S, Grigorov I. Modulation of diabetes-related liver injury by the HMGB1/TLR4 inflammatory pathway.. in Journal of Physiology and Biochemistry. 2018;74(2):345-358.
doi:10.1007/s13105-018-0626-0 .

Jovanović Stojanov, Sofija, Martinović, Vesna, Bogojević, Desanka, Poznanović, Goran, Petrović, Anja, Ivanović Matić, Svetlana, Grigorov, Ilijana, "Modulation of diabetes-related liver injury by the HMGB1/TLR4 inflammatory pathway." in Journal of Physiology and Biochemistry, 74, no. 2 (2018):345-358,
https://doi.org/10.1007/s13105-018-0626-0 . .

TY  - CONF
AU  - Jovanović Stojanov, Sofija
AU  - Grigorov, Ilijana
AU  - Petrović, Anja
AU  - Bogojević, Desanka
AU  - Ivanović Matić, Svetlana
AU  - Martinović, Vesna
PY  - 2017
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5246
AB  - Introduction: Oxidative stress and chronic low-grade inflammation in diabetes leads to liver injury. During diabetes, extracellular level of high-mobility group box-1 (HMGB1) protein increases. Considering that extracellular HMGB1 (eHMGB1) protein functions as an pro-inflammatory mediator, triggering inflammatory responses by promoting the expression of inflammatory cytokines, the aim of this study was to investigate its contribution to the maintenance of inflammatory condition in the liver of diabetic rats. This may help to better understand diabetes-induced liver pathologies and potentially provide target to develop efficient therapies. Methods: Diabetes was induced by a single intraperitoneal (ip) injection of STZ (65 mg/kg). Inflammatory status in the rat liver was determined in the fourth week after diabetes induction by measuring expression of pro-inflammatory cytokines (TNFα, IL- 6) and related production of anti-inflammatory protein haptoglobin (Hp). We also studied the effects of HMGB1 on inflammation through its interaction with TLR4 and related downstream signaling pathways in terms of inhibited HMGB1 secretion in diabetic rats by ethyl pyruvate (EP) treatment (80 mg/kg/ip/daily). Results: The results show that decrease in eHMGB1 expression caused by EP treatment, correlates with reduced level of TNFα, IL-6 and Hp in the serum and liver of diabetic rats. These changes are in accordance with significant decrease in HMGB1/TLR4 interaction and decreased activation of MAPK (p38, ERK, JNK), NF-κB p65 and JAK1/STAT3 signaling pathways in diabetic liver. Conclusion: In diabetic liver eHMGB1 is involved in the inflammatory response dually. It acts pro-inflammatory by enhancing production of inflammatory mediators and anti-inflammatory by increasing Hp expression.
PB  - Belgrade: University of Belgrade, Faculty of Biology
C3  - Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.
T1  - Pro-inflamatory and anti-inflamatory role of HMGB1 in the liver of diabetic rats
SP  - 44
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5246
ER  - 

@conference{
author = "Jovanović Stojanov, Sofija and Grigorov, Ilijana and Petrović, Anja and Bogojević, Desanka and Ivanović Matić, Svetlana and Martinović, Vesna",
year = "2017",
abstract = "Introduction: Oxidative stress and chronic low-grade inflammation in diabetes leads to liver injury. During diabetes, extracellular level of high-mobility group box-1 (HMGB1) protein increases. Considering that extracellular HMGB1 (eHMGB1) protein functions as an pro-inflammatory mediator, triggering inflammatory responses by promoting the expression of inflammatory cytokines, the aim of this study was to investigate its contribution to the maintenance of inflammatory condition in the liver of diabetic rats. This may help to better understand diabetes-induced liver pathologies and potentially provide target to develop efficient therapies. Methods: Diabetes was induced by a single intraperitoneal (ip) injection of STZ (65 mg/kg). Inflammatory status in the rat liver was determined in the fourth week after diabetes induction by measuring expression of pro-inflammatory cytokines (TNFα, IL- 6) and related production of anti-inflammatory protein haptoglobin (Hp). We also studied the effects of HMGB1 on inflammation through its interaction with TLR4 and related downstream signaling pathways in terms of inhibited HMGB1 secretion in diabetic rats by ethyl pyruvate (EP) treatment (80 mg/kg/ip/daily). Results: The results show that decrease in eHMGB1 expression caused by EP treatment, correlates with reduced level of TNFα, IL-6 and Hp in the serum and liver of diabetic rats. These changes are in accordance with significant decrease in HMGB1/TLR4 interaction and decreased activation of MAPK (p38, ERK, JNK), NF-κB p65 and JAK1/STAT3 signaling pathways in diabetic liver. Conclusion: In diabetic liver eHMGB1 is involved in the inflammatory response dually. It acts pro-inflammatory by enhancing production of inflammatory mediators and anti-inflammatory by increasing Hp expression.",
publisher = "Belgrade: University of Belgrade, Faculty of Biology",
journal = "Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.",
title = "Pro-inflamatory and anti-inflamatory role of HMGB1 in the liver of diabetic rats",
pages = "44",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5246"
}

Jovanović Stojanov, S., Grigorov, I., Petrović, A., Bogojević, D., Ivanović Matić, S.,& Martinović, V.. (2017). Pro-inflamatory and anti-inflamatory role of HMGB1 in the liver of diabetic rats. in Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.
Belgrade: University of Belgrade, Faculty of Biology., 44.
https://hdl.handle.net/21.15107/rcub_ibiss_5246

Jovanović Stojanov S, Grigorov I, Petrović A, Bogojević D, Ivanović Matić S, Martinović V. Pro-inflamatory and anti-inflamatory role of HMGB1 in the liver of diabetic rats. in Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.. 2017;:44.
https://hdl.handle.net/21.15107/rcub_ibiss_5246 .

Jovanović Stojanov, Sofija, Grigorov, Ilijana, Petrović, Anja, Bogojević, Desanka, Ivanović Matić, Svetlana, Martinović, Vesna, "Pro-inflamatory and anti-inflamatory role of HMGB1 in the liver of diabetic rats" in Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia. (2017):44,
https://hdl.handle.net/21.15107/rcub_ibiss_5246 .

TY  - CONF
AU  - Petrović, Anja
AU  - Ivanović Matić, Svetlana
AU  - Bogojević, Desanka
AU  - Martinović, Vesna
AU  - Korać, Aleksandra
AU  - Jovanović Stojanov, Sofija
AU  - Stevanović, Jelena
AU  - Grigorov, Ilijana
PY  - 2017
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5244
AB  - Introduction: Hepatocellular death is the main trigger of liver disease. Since diabetic patients are very prone to liver diseases there is a urgent need to identify key regulators of cell death processes. High-mobility group box protein 1 (HMGB1) is a non-histone nuclear protein with a role in apoptotic and autophagic activation when it is present in cytosol and extracellular space. The aim of this study was to elucidate HMGB1 contribution to liver injury trough activation of apoptosis and autophagy in streptozotocin (STZ)-induced diabetic rats since the role of HMGB1 in hepatic cell death during diabetes is partially known. Methods: Diabetes was induced with a single intraperitoneal (i.p.) injection of STZ (65 mg/kg). Inhibition of HMGB1 release was achieved by ethyl pyruvate (80 mg/kg/i.p./daily). We followed changes in expression of serum and cytosolic HMGB1 and its interaction with TLR4 and RAGE and how these changes affect on apoptotic and autophagic activity and liver morphology. Results: In the serum of diabetic rats elevated levels of HMGB1 were accompanied by increased HMGB1 interactions with TLR4 and RAGE receptors. Enhancement in these interactions led to increased activity of both apoptotic and autophagic signaling pathways resulting in altered liver morphology and acummulation of autophagosomes in hepatocytes. Inhibition of HMGB1 release caused reduction in apoptotic and autophagic activity which resulted in preservation of normal liver architecture and decreased number of autophagosomes. Conclusion: HMGB1 causes liver damage through activation of apoptosis and autophagy, therefore it’s a suitable new target for prevention of liver diseases in diabetic patients.
PB  - Belgrade: University of Belgrade, Faculty of Biology
C3  - Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.
T1  - Inhibition of HMGB1 release decreases both apoptopic and autophagic activity in the hepatocytes and reduce liver injury in streptozotocin treated rats
SP  - 65
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5244
ER  - 

@conference{
author = "Petrović, Anja and Ivanović Matić, Svetlana and Bogojević, Desanka and Martinović, Vesna and Korać, Aleksandra and Jovanović Stojanov, Sofija and Stevanović, Jelena and Grigorov, Ilijana",
year = "2017",
abstract = "Introduction: Hepatocellular death is the main trigger of liver disease. Since diabetic patients are very prone to liver diseases there is a urgent need to identify key regulators of cell death processes. High-mobility group box protein 1 (HMGB1) is a non-histone nuclear protein with a role in apoptotic and autophagic activation when it is present in cytosol and extracellular space. The aim of this study was to elucidate HMGB1 contribution to liver injury trough activation of apoptosis and autophagy in streptozotocin (STZ)-induced diabetic rats since the role of HMGB1 in hepatic cell death during diabetes is partially known. Methods: Diabetes was induced with a single intraperitoneal (i.p.) injection of STZ (65 mg/kg). Inhibition of HMGB1 release was achieved by ethyl pyruvate (80 mg/kg/i.p./daily). We followed changes in expression of serum and cytosolic HMGB1 and its interaction with TLR4 and RAGE and how these changes affect on apoptotic and autophagic activity and liver morphology. Results: In the serum of diabetic rats elevated levels of HMGB1 were accompanied by increased HMGB1 interactions with TLR4 and RAGE receptors. Enhancement in these interactions led to increased activity of both apoptotic and autophagic signaling pathways resulting in altered liver morphology and acummulation of autophagosomes in hepatocytes. Inhibition of HMGB1 release caused reduction in apoptotic and autophagic activity which resulted in preservation of normal liver architecture and decreased number of autophagosomes. Conclusion: HMGB1 causes liver damage through activation of apoptosis and autophagy, therefore it’s a suitable new target for prevention of liver diseases in diabetic patients.",
publisher = "Belgrade: University of Belgrade, Faculty of Biology",
journal = "Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.",
title = "Inhibition of HMGB1 release decreases both apoptopic and autophagic activity in the hepatocytes and reduce liver injury in streptozotocin treated rats",
pages = "65",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5244"
}

Petrović, A., Ivanović Matić, S., Bogojević, D., Martinović, V., Korać, A., Jovanović Stojanov, S., Stevanović, J.,& Grigorov, I.. (2017). Inhibition of HMGB1 release decreases both apoptopic and autophagic activity in the hepatocytes and reduce liver injury in streptozotocin treated rats. in Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.
Belgrade: University of Belgrade, Faculty of Biology., 65.
https://hdl.handle.net/21.15107/rcub_ibiss_5244

Petrović A, Ivanović Matić S, Bogojević D, Martinović V, Korać A, Jovanović Stojanov S, Stevanović J, Grigorov I. Inhibition of HMGB1 release decreases both apoptopic and autophagic activity in the hepatocytes and reduce liver injury in streptozotocin treated rats. in Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.. 2017;:65.
https://hdl.handle.net/21.15107/rcub_ibiss_5244 .

Petrović, Anja, Ivanović Matić, Svetlana, Bogojević, Desanka, Martinović, Vesna, Korać, Aleksandra, Jovanović Stojanov, Sofija, Stevanović, Jelena, Grigorov, Ilijana, "Inhibition of HMGB1 release decreases both apoptopic and autophagic activity in the hepatocytes and reduce liver injury in streptozotocin treated rats" in Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia. (2017):65,
https://hdl.handle.net/21.15107/rcub_ibiss_5244 .

TY  - CONF
AU  - Martinović, Vesna
AU  - Jovanović Stojanov, Sofija
AU  - Bogojević, Desanka
AU  - Ivanović Matić, Svetlana
AU  - Petrović, Anja
AU  - Poznanović, Goran
AU  - Grigorov, Ilijana
PY  - 2017
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5245
AB  - Introduction: Oxidative stress and inflammation are involved in the pathogenesis of diabetes. Previously, we showed that melatonin exerts potent anti-oxidative and anti-inflammatory actions in the liver of streptozotocin (STZ)-induced diabetic rats, thus correcting diabetes-associated abnormalities. The concept of a liver-spleen axis has been proposed as an intersection linking immunity and metabolism in various conditions, including chronic liver diseases. We therefore compared the effect of melatonin on oxidative stress and the inflammatory response in the liver and spleen of STZ-induced diabetic rats. Methods: Male Wistar rats were injected with 65 mg/kg STZ to induce diabetes. Melatonin was administrated daily (0.2 mg/kg/i.p) until the end of the study at 4 weeks after diabetes induction. Oxidative stress was assessed by measuring the level of lipid peroxidation and the changes in antioxidative enzyme activities. Inflammation was evaluated by examining the levels of proinflammatory cytokines, inflammatory mediators and the acute-phase protein haptoglobin (Hp). Results: In both tissues, melatonin lowered oxidative stress, which was observed as a decrease in lipid peroxidation and increased expression and activity of CAT, MnSOD and CuZnSOD. By suppressing the activation of NF-κB p65 and MAPK (p38, JNK, ERK) signaling cascades and by decreasing the production of TNF-α, IL-6, HMGB1 and Hp, melatonin also reduced inflammation. Conclusion: Melatonin stimulated the antioxidative defense in both, the spleen and liver of diabetic rats and attenuated inflammation via the same molecular mechanisms.
PB  - Belgrade: University of Belgrade, Faculty of Biology
C3  - Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.
T1  - Effect of melatonin on oxdative and inflammatory stress in spleen and liver of streptozotocin -induced diabetic rats
SP  - 55
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5245
ER  - 

@conference{
author = "Martinović, Vesna and Jovanović Stojanov, Sofija and Bogojević, Desanka and Ivanović Matić, Svetlana and Petrović, Anja and Poznanović, Goran and Grigorov, Ilijana",
year = "2017",
abstract = "Introduction: Oxidative stress and inflammation are involved in the pathogenesis of diabetes. Previously, we showed that melatonin exerts potent anti-oxidative and anti-inflammatory actions in the liver of streptozotocin (STZ)-induced diabetic rats, thus correcting diabetes-associated abnormalities. The concept of a liver-spleen axis has been proposed as an intersection linking immunity and metabolism in various conditions, including chronic liver diseases. We therefore compared the effect of melatonin on oxidative stress and the inflammatory response in the liver and spleen of STZ-induced diabetic rats. Methods: Male Wistar rats were injected with 65 mg/kg STZ to induce diabetes. Melatonin was administrated daily (0.2 mg/kg/i.p) until the end of the study at 4 weeks after diabetes induction. Oxidative stress was assessed by measuring the level of lipid peroxidation and the changes in antioxidative enzyme activities. Inflammation was evaluated by examining the levels of proinflammatory cytokines, inflammatory mediators and the acute-phase protein haptoglobin (Hp). Results: In both tissues, melatonin lowered oxidative stress, which was observed as a decrease in lipid peroxidation and increased expression and activity of CAT, MnSOD and CuZnSOD. By suppressing the activation of NF-κB p65 and MAPK (p38, JNK, ERK) signaling cascades and by decreasing the production of TNF-α, IL-6, HMGB1 and Hp, melatonin also reduced inflammation. Conclusion: Melatonin stimulated the antioxidative defense in both, the spleen and liver of diabetic rats and attenuated inflammation via the same molecular mechanisms.",
publisher = "Belgrade: University of Belgrade, Faculty of Biology",
journal = "Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.",
title = "Effect of melatonin on oxdative and inflammatory stress in spleen and liver of streptozotocin -induced diabetic rats",
pages = "55",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5245"
}

Martinović, V., Jovanović Stojanov, S., Bogojević, D., Ivanović Matić, S., Petrović, A., Poznanović, G.,& Grigorov, I.. (2017). Effect of melatonin on oxdative and inflammatory stress in spleen and liver of streptozotocin -induced diabetic rats. in Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.
Belgrade: University of Belgrade, Faculty of Biology., 55.
https://hdl.handle.net/21.15107/rcub_ibiss_5245

Martinović V, Jovanović Stojanov S, Bogojević D, Ivanović Matić S, Petrović A, Poznanović G, Grigorov I. Effect of melatonin on oxdative and inflammatory stress in spleen and liver of streptozotocin -induced diabetic rats. in Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia.. 2017;:55.
https://hdl.handle.net/21.15107/rcub_ibiss_5245 .

Martinović, Vesna, Jovanović Stojanov, Sofija, Bogojević, Desanka, Ivanović Matić, Svetlana, Petrović, Anja, Poznanović, Goran, Grigorov, Ilijana, "Effect of melatonin on oxdative and inflammatory stress in spleen and liver of streptozotocin -induced diabetic rats" in Book of Abstracts: 1st Congress of Molecular Biologists of Serbia: CoMBoS; 2017 Sep 20-21; Belgrade, Serbia. (2017):55,
https://hdl.handle.net/21.15107/rcub_ibiss_5245 .

TY  - JOUR
AU  - Petrović, Anja
AU  - Bogojević, Desanka
AU  - Korać, Aleksandra
AU  - Golić, Igor
AU  - Jovanović Stojanov, Sofija
AU  - Martinović, Vesna
AU  - Ivanović Matić, Svetlana
AU  - Stevanović, Jelena
AU  - Poznanović, Goran
AU  - Grigorov, Ilijana
PY  - 2017
UR  - http://link.springer.com/10.1007/s13105-017-0574-0
UR  - http://www.ncbi.nlm.nih.gov/pubmed/28695466
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2787
AB  - The progression of oxidative stress, resulting cell damage, and cell death underlies the etiology of liver damage/dysfunction as a complication of diabetes. High-mobility group box 1 (HMGB1) protein, a chromatin-binding nuclear protein and damage-associated molecular pattern molecule, is integral to oxidative stress and signaling pathways regulating cell death and cell survival. We previously found that in streptozotocin (STZ)-induced diabetic rats, reduction of oxidative stress after melatonin administration lowered necrotic cell death and increased expression of HMGB1 and hepatocellular damage. In the present study, we examined whether alleviation of diabetes-attendant oxidative stress and ensuing change in HMGB1 expression influence the dynamic equilibrium between apoptosis/autophagy and liver damage. We observed that elevated HMGB1 protein levels in diabetic rat liver accompanied increased interactions of HMGB1 with TLR4 and RAGE, and activation of the intrinsic apoptotic pathway and Beclin 1-dependent autophagy. The absence of p62 degradation in diabetic rat liver pointed to defective autophagy which was responsible for lower autophagosome/autophagolysosome formation and an increased apoptosis/autophagy ratio. Compared to diabetic rats, in melatonin-treated diabetic rats, the structure of liver cells was preserved, HMGB1/TLR4 interaction and downstream apoptotic signaling were significantly reduced, HMGB1/Beclin 1 colocalization and interactions were augmented and Beclin 1-mediated autophagy, mithophagy in particular, were increased. We concluded that in mild oxidative stress, HMGB1 is cytoprotective, whereas in intense oxidative stress, HMGB1 actions promote cell death and liver damage. Since reduced HMGB1 binds to RAGE but not to TLR4, redox modification of HMGB1 as a mechanism regulating the cross-talk between apoptosis and autophagy in diabetes is discussed.
T2  - Journal of Physiology and Biochemistry
T1  - Oxidative stress-dependent contribution of HMGB1 to the interplay between apoptosis and autophagy in diabetic rat liver.
DO  - 10.1007/s13105-017-0574-0
ER  - 

@article{
author = "Petrović, Anja and Bogojević, Desanka and Korać, Aleksandra and Golić, Igor and Jovanović Stojanov, Sofija and Martinović, Vesna and Ivanović Matić, Svetlana and Stevanović, Jelena and Poznanović, Goran and Grigorov, Ilijana",
year = "2017",
abstract = "The progression of oxidative stress, resulting cell damage, and cell death underlies the etiology of liver damage/dysfunction as a complication of diabetes. High-mobility group box 1 (HMGB1) protein, a chromatin-binding nuclear protein and damage-associated molecular pattern molecule, is integral to oxidative stress and signaling pathways regulating cell death and cell survival. We previously found that in streptozotocin (STZ)-induced diabetic rats, reduction of oxidative stress after melatonin administration lowered necrotic cell death and increased expression of HMGB1 and hepatocellular damage. In the present study, we examined whether alleviation of diabetes-attendant oxidative stress and ensuing change in HMGB1 expression influence the dynamic equilibrium between apoptosis/autophagy and liver damage. We observed that elevated HMGB1 protein levels in diabetic rat liver accompanied increased interactions of HMGB1 with TLR4 and RAGE, and activation of the intrinsic apoptotic pathway and Beclin 1-dependent autophagy. The absence of p62 degradation in diabetic rat liver pointed to defective autophagy which was responsible for lower autophagosome/autophagolysosome formation and an increased apoptosis/autophagy ratio. Compared to diabetic rats, in melatonin-treated diabetic rats, the structure of liver cells was preserved, HMGB1/TLR4 interaction and downstream apoptotic signaling were significantly reduced, HMGB1/Beclin 1 colocalization and interactions were augmented and Beclin 1-mediated autophagy, mithophagy in particular, were increased. We concluded that in mild oxidative stress, HMGB1 is cytoprotective, whereas in intense oxidative stress, HMGB1 actions promote cell death and liver damage. Since reduced HMGB1 binds to RAGE but not to TLR4, redox modification of HMGB1 as a mechanism regulating the cross-talk between apoptosis and autophagy in diabetes is discussed.",
journal = "Journal of Physiology and Biochemistry",
title = "Oxidative stress-dependent contribution of HMGB1 to the interplay between apoptosis and autophagy in diabetic rat liver.",
doi = "10.1007/s13105-017-0574-0"
}

Petrović, A., Bogojević, D., Korać, A., Golić, I., Jovanović Stojanov, S., Martinović, V., Ivanović Matić, S., Stevanović, J., Poznanović, G.,& Grigorov, I.. (2017). Oxidative stress-dependent contribution of HMGB1 to the interplay between apoptosis and autophagy in diabetic rat liver.. in Journal of Physiology and Biochemistry.
https://doi.org/10.1007/s13105-017-0574-0

Petrović A, Bogojević D, Korać A, Golić I, Jovanović Stojanov S, Martinović V, Ivanović Matić S, Stevanović J, Poznanović G, Grigorov I. Oxidative stress-dependent contribution of HMGB1 to the interplay between apoptosis and autophagy in diabetic rat liver.. in Journal of Physiology and Biochemistry. 2017;.
doi:10.1007/s13105-017-0574-0 .

Petrović, Anja, Bogojević, Desanka, Korać, Aleksandra, Golić, Igor, Jovanović Stojanov, Sofija, Martinović, Vesna, Ivanović Matić, Svetlana, Stevanović, Jelena, Poznanović, Goran, Grigorov, Ilijana, "Oxidative stress-dependent contribution of HMGB1 to the interplay between apoptosis and autophagy in diabetic rat liver." in Journal of Physiology and Biochemistry (2017),
https://doi.org/10.1007/s13105-017-0574-0 . .