TY  - JOUR
AU  - Todorović, Zoran
AU  - Đurašević, Siniša
AU  - Stojković, Maja
AU  - Grigorov, Ilijana
AU  - Pavlović, Slađan
AU  - Jasnić, Nebojša
AU  - Tosti, Tomislav
AU  - Bjekić Macut, Jelica
AU  - Thiemermann, Christoph
AU  - Đorđević, Jelena
PY  - 2021
UR  - https://www.mdpi.com/1422-0067/22/6/2798
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4162
AB  - Lipids play an essential role in both tissue protection and damage. Tissue ischemia creates anaerobic conditions in which enzyme inactivation occurs, and reperfusion can initiate oxidative stress that leads to harmful changes in membrane lipids, the formation of aldehydes, and chain damage until cell death. The critical event in such a series of harmful events in the cell is the unwanted accumulation of fatty acids that leads to lipotoxicity. Lipid analysis provides additional insight into the pathogenesis of ischemia/reperfusion (I/R) disorders and reveals new targets for drug action. The profile of changes in the composition of fatty acids in the cell, as well as the time course of these changes, indicate both the mechanism of damage and new therapeutic possibilities. A therapeutic approach to reperfusion lipotoxicity involves attenuation of fatty acids overload, i.e., their transport to adipose tissue and/or inhibition of the adverse effects of fatty acids on cell damage and death. The latter option involves using PPAR agonists and drugs that modulate the transport of fatty acids via carnitine into the interior of the mitochondria or the redirection of long-chain fatty acids to peroxisomes.
PB  - Multidisciplinary Digital Publishing Institute
T2  - International Journal of Molecular Sciences
T1  - Lipidomics Provides New Insight into Pathogenesis and Therapeutic Targets of the Ischemia—Reperfusion Injury
IS  - 6
VL  - 22
DO  - 10.3390/ijms22062798
SP  - 2798
ER  - 

@article{
author = "Todorović, Zoran and Đurašević, Siniša and Stojković, Maja and Grigorov, Ilijana and Pavlović, Slađan and Jasnić, Nebojša and Tosti, Tomislav and Bjekić Macut, Jelica and Thiemermann, Christoph and Đorđević, Jelena",
year = "2021",
abstract = "Lipids play an essential role in both tissue protection and damage. Tissue ischemia creates anaerobic conditions in which enzyme inactivation occurs, and reperfusion can initiate oxidative stress that leads to harmful changes in membrane lipids, the formation of aldehydes, and chain damage until cell death. The critical event in such a series of harmful events in the cell is the unwanted accumulation of fatty acids that leads to lipotoxicity. Lipid analysis provides additional insight into the pathogenesis of ischemia/reperfusion (I/R) disorders and reveals new targets for drug action. The profile of changes in the composition of fatty acids in the cell, as well as the time course of these changes, indicate both the mechanism of damage and new therapeutic possibilities. A therapeutic approach to reperfusion lipotoxicity involves attenuation of fatty acids overload, i.e., their transport to adipose tissue and/or inhibition of the adverse effects of fatty acids on cell damage and death. The latter option involves using PPAR agonists and drugs that modulate the transport of fatty acids via carnitine into the interior of the mitochondria or the redirection of long-chain fatty acids to peroxisomes.",
publisher = "Multidisciplinary Digital Publishing Institute",
journal = "International Journal of Molecular Sciences",
title = "Lipidomics Provides New Insight into Pathogenesis and Therapeutic Targets of the Ischemia—Reperfusion Injury",
number = "6",
volume = "22",
doi = "10.3390/ijms22062798",
pages = "2798"
}

Todorović, Z., Đurašević, S., Stojković, M., Grigorov, I., Pavlović, S., Jasnić, N., Tosti, T., Bjekić Macut, J., Thiemermann, C.,& Đorđević, J.. (2021). Lipidomics Provides New Insight into Pathogenesis and Therapeutic Targets of the Ischemia—Reperfusion Injury. in International Journal of Molecular Sciences
Multidisciplinary Digital Publishing Institute., 22(6), 2798.
https://doi.org/10.3390/ijms22062798

Todorović Z, Đurašević S, Stojković M, Grigorov I, Pavlović S, Jasnić N, Tosti T, Bjekić Macut J, Thiemermann C, Đorđević J. Lipidomics Provides New Insight into Pathogenesis and Therapeutic Targets of the Ischemia—Reperfusion Injury. in International Journal of Molecular Sciences. 2021;22(6):2798.
doi:10.3390/ijms22062798 .

Todorović, Zoran, Đurašević, Siniša, Stojković, Maja, Grigorov, Ilijana, Pavlović, Slađan, Jasnić, Nebojša, Tosti, Tomislav, Bjekić Macut, Jelica, Thiemermann, Christoph, Đorđević, Jelena, "Lipidomics Provides New Insight into Pathogenesis and Therapeutic Targets of the Ischemia—Reperfusion Injury" in International Journal of Molecular Sciences, 22, no. 6 (2021):2798,
https://doi.org/10.3390/ijms22062798 . .

TY  - JOUR
AU  - Đurašević, Siniša
AU  - Pejić, Snežana
AU  - Grigorov, Ilijana
AU  - Nikolić, Gorana
AU  - Mitić-Ćulafić, Dragana
AU  - Dragićević, Milan
AU  - Đorđević, Jelena
AU  - Todorović Vukotić, Nevena
AU  - Đorđević, Neda
AU  - Todorović, Ana
AU  - Drakulić, Dunja
AU  - Veljković, Filip
AU  - Pajović, Snežana B.
AU  - Todorović, Zoran
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4289
AB  - Thioacetamide (TAA) is widely used to study liver toxicity accompanied by oxidative stress, inflammation, cell necrosis, fibrosis, cholestasis, and hepatocellular carcinoma. As an efficient free radical’s scavenger, C60 fullerene is considered a potential liver-protective agent in chemically-induced liver injury. In the present work, we examined the hepatoprotective effects of two C60 doses dissolved in virgin olive oil against TAA-induced hepatotoxicity in rats. We showed that TAA-induced increase in liver oxidative stress, judged by the changes in the activities of SOD, CAT, GPx, GR, GST, the content of GSH and 4-HNE, and expression of HO-1, MnSOD, and CuZnSOD, was more effectively ameliorated with a lower C60 dose. Improvement in liver antioxidative status caused by C60 was accompanied by a decrease in liver HMGB1 expression and an increase in nuclear Nrf2/NF-κB p65 ratio, suggesting a reduction in inflammation, necrosis and fibrosis. These results were in accordance with liver histology analysis, liver comet assay, and changes in serum levels of ALT, AST, and AP. The changes observed in gut microbiome support detrimental effects of TAA and hepatoprotective effects of low C60 dose. Less protective effects of a higher C60 dose could be a consequence of its enhanced aggregation and related pro-oxidant role.
PB  - MDPI
T2  - Antioxidants
T1  - Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes
IS  - 6
VL  - 10
DO  - 10.3390/antiox10060911
SP  - 911
ER  - 

@article{
author = "Đurašević, Siniša and Pejić, Snežana and Grigorov, Ilijana and Nikolić, Gorana and Mitić-Ćulafić, Dragana and Dragićević, Milan and Đorđević, Jelena and Todorović Vukotić, Nevena and Đorđević, Neda and Todorović, Ana and Drakulić, Dunja and Veljković, Filip and Pajović, Snežana B. and Todorović, Zoran",
year = "2021",
abstract = "Thioacetamide (TAA) is widely used to study liver toxicity accompanied by oxidative stress, inflammation, cell necrosis, fibrosis, cholestasis, and hepatocellular carcinoma. As an efficient free radical’s scavenger, C60 fullerene is considered a potential liver-protective agent in chemically-induced liver injury. In the present work, we examined the hepatoprotective effects of two C60 doses dissolved in virgin olive oil against TAA-induced hepatotoxicity in rats. We showed that TAA-induced increase in liver oxidative stress, judged by the changes in the activities of SOD, CAT, GPx, GR, GST, the content of GSH and 4-HNE, and expression of HO-1, MnSOD, and CuZnSOD, was more effectively ameliorated with a lower C60 dose. Improvement in liver antioxidative status caused by C60 was accompanied by a decrease in liver HMGB1 expression and an increase in nuclear Nrf2/NF-κB p65 ratio, suggesting a reduction in inflammation, necrosis and fibrosis. These results were in accordance with liver histology analysis, liver comet assay, and changes in serum levels of ALT, AST, and AP. The changes observed in gut microbiome support detrimental effects of TAA and hepatoprotective effects of low C60 dose. Less protective effects of a higher C60 dose could be a consequence of its enhanced aggregation and related pro-oxidant role.",
publisher = "MDPI",
journal = "Antioxidants",
title = "Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes",
number = "6",
volume = "10",
doi = "10.3390/antiox10060911",
pages = "911"
}

Đurašević, S., Pejić, S., Grigorov, I., Nikolić, G., Mitić-Ćulafić, D., Dragićević, M., Đorđević, J., Todorović Vukotić, N., Đorđević, N., Todorović, A., Drakulić, D., Veljković, F., Pajović, S. B.,& Todorović, Z.. (2021). Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes. in Antioxidants
MDPI., 10(6), 911.
https://doi.org/10.3390/antiox10060911

Đurašević S, Pejić S, Grigorov I, Nikolić G, Mitić-Ćulafić D, Dragićević M, Đorđević J, Todorović Vukotić N, Đorđević N, Todorović A, Drakulić D, Veljković F, Pajović SB, Todorović Z. Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes. in Antioxidants. 2021;10(6):911.
doi:10.3390/antiox10060911 .

Đurašević, Siniša, Pejić, Snežana, Grigorov, Ilijana, Nikolić, Gorana, Mitić-Ćulafić, Dragana, Dragićević, Milan, Đorđević, Jelena, Todorović Vukotić, Nevena, Đorđević, Neda, Todorović, Ana, Drakulić, Dunja, Veljković, Filip, Pajović, Snežana B., Todorović, Zoran, "Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes" in Antioxidants, 10, no. 6 (2021):911,
https://doi.org/10.3390/antiox10060911 . .

TY  - CONF
AU  - Todorović, Zoran
AU  - Đurašević, Siniša
AU  - Tosti, Tomislav
AU  - Lakić, Iva
AU  - Grigorov, Ilijana
AU  - Đorđević, Jelena
AU  - Đukanović, Nina
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4895
AB  - Lipidomics deals with small molecules metabolomes with a mass lower than 1500. In recent years, the crucial role of lipidomes in the pathogenesis and therapy of cardiovascular events has become increasingly apparent.1-3 For example, ischemia-reperfusion (IR) injury can initiate oxidative stress that leads to harmful changes in membrane lipids, with an unwanted accumulation of fatty acids that leads to lipotoxicity. Lipid analysis provides additional insight into the pathogenesis of IR disorders and reveals new targets for drug action. A therapeutic approach to reperfusion lipotoxicity involves attenuation of fatty acids overload, i.e., their transport to adipose tissue and/or inhibition of the adverse effects of fatty acids on cell damage and death. The latter option involves using PPAR agonists and drugs that modulate the transport of fatty acids via carnitine into the interior of the mitochondria or the redirection of long-chain fatty acids to peroxisomes. Regarding platelet functions, polyunsaturated fatty acids play a role in increasing platelet reactivity, and that the prothrombotic phenotype plays a crucial role in the occurrence of major adverse cardiovascular events. The ongoing increase in cardiovascular diseases incidence emphasizes the importance of research linking lipids and platelet function. In particular, the rebound phenomenon that accompanies clopidogrel discontinuation in patients receiving dual antiplatelet therapy has been associated with changes in the lipid profile. Our many years of research underline the importance of reduced HDL values for the risk of such a rebound effect and the occurrence of thromboembolic events. Lipids are otherwise a heterogeneous group of molecules, and their signaling molecules are not deposited but formed “on-demand” in the cell. On the other hand, exosomes transmit lipid signals between cells, and the profile of such changes can be monitored by lipidomics. Changes in the lipid profile are organ-specific and may indicate new drug action targets.
PB  - Banja Luka: Association of Medical Doctors
PB  - Banja Luka: Faculty of Medicine, University of Banja Luka
C3  - 7th Meeting of the European section and 8th Meeting of the North American section of the International academy of cardiovascular sciences (IACS); 2021 Sep 20-23; Banja Luka, Bosnia and Herzegovina
T1  - Lipidomics as a Novel Tool in Cardiovascular Research
SP  - 87
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4895
ER  - 

@conference{
author = "Todorović, Zoran and Đurašević, Siniša and Tosti, Tomislav and Lakić, Iva and Grigorov, Ilijana and Đorđević, Jelena and Đukanović, Nina",
year = "2021",
abstract = "Lipidomics deals with small molecules metabolomes with a mass lower than 1500. In recent years, the crucial role of lipidomes in the pathogenesis and therapy of cardiovascular events has become increasingly apparent.1-3 For example, ischemia-reperfusion (IR) injury can initiate oxidative stress that leads to harmful changes in membrane lipids, with an unwanted accumulation of fatty acids that leads to lipotoxicity. Lipid analysis provides additional insight into the pathogenesis of IR disorders and reveals new targets for drug action. A therapeutic approach to reperfusion lipotoxicity involves attenuation of fatty acids overload, i.e., their transport to adipose tissue and/or inhibition of the adverse effects of fatty acids on cell damage and death. The latter option involves using PPAR agonists and drugs that modulate the transport of fatty acids via carnitine into the interior of the mitochondria or the redirection of long-chain fatty acids to peroxisomes. Regarding platelet functions, polyunsaturated fatty acids play a role in increasing platelet reactivity, and that the prothrombotic phenotype plays a crucial role in the occurrence of major adverse cardiovascular events. The ongoing increase in cardiovascular diseases incidence emphasizes the importance of research linking lipids and platelet function. In particular, the rebound phenomenon that accompanies clopidogrel discontinuation in patients receiving dual antiplatelet therapy has been associated with changes in the lipid profile. Our many years of research underline the importance of reduced HDL values for the risk of such a rebound effect and the occurrence of thromboembolic events. Lipids are otherwise a heterogeneous group of molecules, and their signaling molecules are not deposited but formed “on-demand” in the cell. On the other hand, exosomes transmit lipid signals between cells, and the profile of such changes can be monitored by lipidomics. Changes in the lipid profile are organ-specific and may indicate new drug action targets.",
publisher = "Banja Luka: Association of Medical Doctors, Banja Luka: Faculty of Medicine, University of Banja Luka",
journal = "7th Meeting of the European section and 8th Meeting of the North American section of the International academy of cardiovascular sciences (IACS); 2021 Sep 20-23; Banja Luka, Bosnia and Herzegovina",
title = "Lipidomics as a Novel Tool in Cardiovascular Research",
pages = "87",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4895"
}

Todorović, Z., Đurašević, S., Tosti, T., Lakić, I., Grigorov, I., Đorđević, J.,& Đukanović, N.. (2021). Lipidomics as a Novel Tool in Cardiovascular Research. in 7th Meeting of the European section and 8th Meeting of the North American section of the International academy of cardiovascular sciences (IACS); 2021 Sep 20-23; Banja Luka, Bosnia and Herzegovina
Banja Luka: Association of Medical Doctors., 87.
https://hdl.handle.net/21.15107/rcub_ibiss_4895

Todorović Z, Đurašević S, Tosti T, Lakić I, Grigorov I, Đorđević J, Đukanović N. Lipidomics as a Novel Tool in Cardiovascular Research. in 7th Meeting of the European section and 8th Meeting of the North American section of the International academy of cardiovascular sciences (IACS); 2021 Sep 20-23; Banja Luka, Bosnia and Herzegovina. 2021;:87.
https://hdl.handle.net/21.15107/rcub_ibiss_4895 .

Todorović, Zoran, Đurašević, Siniša, Tosti, Tomislav, Lakić, Iva, Grigorov, Ilijana, Đorđević, Jelena, Đukanović, Nina, "Lipidomics as a Novel Tool in Cardiovascular Research" in 7th Meeting of the European section and 8th Meeting of the North American section of the International academy of cardiovascular sciences (IACS); 2021 Sep 20-23; Banja Luka, Bosnia and Herzegovina (2021):87,
https://hdl.handle.net/21.15107/rcub_ibiss_4895 .

TY  - JOUR
AU  - Đurašević, Siniša
AU  - Stojković, Maja
AU  - Bogdanović, Ljiljana
AU  - Pavlović, Slađan
AU  - Borković Mitić, Slavica
AU  - Grigorov, Ilijana
AU  - Bogojević, Desanka
AU  - Jasnić, Nebojša
AU  - Tosti, Tomislav
AU  - Đurović, Saša
AU  - Đorđević, Jelena
AU  - Todorović, Zoran
PY  - 2019
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3519
AB  - Acute renal ischemia/reperfusion (I/R) injury is a clinical condition that is challenging to
treat. Meldonium is an anti-ischemic agent that shifts energy production from fatty acid oxidation
to less oxygen-consuming glycolysis. Thus, in this study we investigated the effects of a four-week
meldonium pre-treatment (300 mg/kg b.m./day) on acute renal I/R in male rats (Wistar strain). Our
results showed that meldonium decreased animal body mass gain, food and water intake, and
carnitine, glucose, and lactic acid kidney content. In kidneys of animals subjected to I/R, meldonium
increased phosphorylation of mitogen-activated protein kinase p38 and protein kinase B, and
increased the expression of nuclear factor erythroid 2-related factor 2 and haeme oxygenase 1,
causing manganese superoxide dismutase expression and activity to increase, as well as lipid
peroxidation, cooper-zinc superoxide dismutase, glutathione peroxidase, and glutathione reductase
activities to decrease. By decreasing the kidney Bax/Bcl2 expression ratio and kidney and serum
high mobility group box 1 protein content, meldonium reduced apoptotic and necrotic events in
I/R, as confirmed by kidney histology. Meldonium increased adrenal noradrenaline content and
serum, adrenal, hepatic, and renal ascorbic/dehydroascorbic acid ratio, which caused complex
changes in renal lipidomics. Taken together, our results have confirmed that meldonium pretreatment protects against I/R-induced oxidative stress and apoptosis/necrosis.
PB  - MDPI
T2  - International Journal of Molecular Sciences
T1  - The effects of meldonium on the renal acute ischemia/reperfusion injury in rats
IS  - 22
VL  - 20
DO  - 10.3390/ijms20225747
SP  - 5747
ER  - 

@article{
author = "Đurašević, Siniša and Stojković, Maja and Bogdanović, Ljiljana and Pavlović, Slađan and Borković Mitić, Slavica and Grigorov, Ilijana and Bogojević, Desanka and Jasnić, Nebojša and Tosti, Tomislav and Đurović, Saša and Đorđević, Jelena and Todorović, Zoran",
year = "2019",
abstract = "Acute renal ischemia/reperfusion (I/R) injury is a clinical condition that is challenging to
treat. Meldonium is an anti-ischemic agent that shifts energy production from fatty acid oxidation
to less oxygen-consuming glycolysis. Thus, in this study we investigated the effects of a four-week
meldonium pre-treatment (300 mg/kg b.m./day) on acute renal I/R in male rats (Wistar strain). Our
results showed that meldonium decreased animal body mass gain, food and water intake, and
carnitine, glucose, and lactic acid kidney content. In kidneys of animals subjected to I/R, meldonium
increased phosphorylation of mitogen-activated protein kinase p38 and protein kinase B, and
increased the expression of nuclear factor erythroid 2-related factor 2 and haeme oxygenase 1,
causing manganese superoxide dismutase expression and activity to increase, as well as lipid
peroxidation, cooper-zinc superoxide dismutase, glutathione peroxidase, and glutathione reductase
activities to decrease. By decreasing the kidney Bax/Bcl2 expression ratio and kidney and serum
high mobility group box 1 protein content, meldonium reduced apoptotic and necrotic events in
I/R, as confirmed by kidney histology. Meldonium increased adrenal noradrenaline content and
serum, adrenal, hepatic, and renal ascorbic/dehydroascorbic acid ratio, which caused complex
changes in renal lipidomics. Taken together, our results have confirmed that meldonium pretreatment protects against I/R-induced oxidative stress and apoptosis/necrosis.",
publisher = "MDPI",
journal = "International Journal of Molecular Sciences",
title = "The effects of meldonium on the renal acute ischemia/reperfusion injury in rats",
number = "22",
volume = "20",
doi = "10.3390/ijms20225747",
pages = "5747"
}

Đurašević, S., Stojković, M., Bogdanović, L., Pavlović, S., Borković Mitić, S., Grigorov, I., Bogojević, D., Jasnić, N., Tosti, T., Đurović, S., Đorđević, J.,& Todorović, Z.. (2019). The effects of meldonium on the renal acute ischemia/reperfusion injury in rats. in International Journal of Molecular Sciences
MDPI., 20(22), 5747.
https://doi.org/10.3390/ijms20225747

Đurašević S, Stojković M, Bogdanović L, Pavlović S, Borković Mitić S, Grigorov I, Bogojević D, Jasnić N, Tosti T, Đurović S, Đorđević J, Todorović Z. The effects of meldonium on the renal acute ischemia/reperfusion injury in rats. in International Journal of Molecular Sciences. 2019;20(22):5747.
doi:10.3390/ijms20225747 .

Đurašević, Siniša, Stojković, Maja, Bogdanović, Ljiljana, Pavlović, Slađan, Borković Mitić, Slavica, Grigorov, Ilijana, Bogojević, Desanka, Jasnić, Nebojša, Tosti, Tomislav, Đurović, Saša, Đorđević, Jelena, Todorović, Zoran, "The effects of meldonium on the renal acute ischemia/reperfusion injury in rats" in International Journal of Molecular Sciences, 20, no. 22 (2019):5747,
https://doi.org/10.3390/ijms20225747 . .