TY  - CONF
AU  - Đurašević, Siniša
AU  - Stojković, Maja
AU  - Bogdanović, Ljiljana
AU  - Grigorov, Ilijana
AU  - Bogojević, Desanka
AU  - Jasnić, Nebojša
AU  - Vujović, Predrag
AU  - Dakić, Tamara
AU  - Todorović, Zoran
AU  - Đorđević, Jelena
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6333
AB  - Acute renal ischemia/reperfusion (I/R) is a temporary restriction of kidney blood supply, followed by blood flow restoration and re-oxygenation. During I/R, decreased oxygen supply disturbs ion transport, intracellular ATP, calcium and pH levels, and numerous signalling pathways. Upon reperfusion, a restoration of oxygen level rises a reactive oxygen species generation, cytokines and chemokines release from activated tissue-resident macrophages, and infiltration of pro-inflammatory neutrophils into ischemic tissues. All these changes result in cell swelling and rupturing, and consequent necrotic or apoptotic cell death. Meldonium is an anti-ischemic drug clinically used to treat myocardial and cerebral ischemia, which acts by shifting energy production from fatty acid oxidation to glycolysis. We investigated the effects of a 4-week meldonium pre-treatment with 300 mg/kg b.m./day of rats subjected to a well-established experimental model of renal I/R, with ischemia lasting for 45 minutes, followed by 4 hours of reperfusion. The degree of apoptosis and necrosis was evaluated by measuring renal pro-apoptotic Bax and anti-apoptotic Bcl-2 ratio, serum and kidney levels of necrotic marker - high mobility group box 1 protein (HMGB1), together with the kidney histology analysis. Our results showed that apoptotic and necrotic cell death occur simultaneously under I/R conditions, judging by the renal Bax/Bcl2 ratio rise (2.7-fold), increase in serum (22%) and renal (30%) levels of HMGB1, as well as severe tubular necrosis with dilatation of the tubular structure, cast formation, tubular lumina dilatation, brush border reduction, and loss in some renal areas cells. Meldonium pretreatment reduced the elevated Bax/Bcl2 ratio by 35%, as well as the serum and renal HMGB1 levels by 20% and notably diminished histological evidence of renal I/R necrotic injury, especially regarding tubular structures. These findings proved that meldonium protects renal cells against I/R-induced necrosis and apoptosis.
PB  - Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade
C3  - Immunology at the Confluence of Multidisciplinary Approaches
T1  - Meldonium prevents acute ishemia/reperfusion inducend-renal cells death in rats
SP  - 86
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6333
ER  - 

@conference{
author = "Đurašević, Siniša and Stojković, Maja and Bogdanović, Ljiljana and Grigorov, Ilijana and Bogojević, Desanka and Jasnić, Nebojša and Vujović, Predrag and Dakić, Tamara and Todorović, Zoran and Đorđević, Jelena",
year = "2019",
abstract = "Acute renal ischemia/reperfusion (I/R) is a temporary restriction of kidney blood supply, followed by blood flow restoration and re-oxygenation. During I/R, decreased oxygen supply disturbs ion transport, intracellular ATP, calcium and pH levels, and numerous signalling pathways. Upon reperfusion, a restoration of oxygen level rises a reactive oxygen species generation, cytokines and chemokines release from activated tissue-resident macrophages, and infiltration of pro-inflammatory neutrophils into ischemic tissues. All these changes result in cell swelling and rupturing, and consequent necrotic or apoptotic cell death. Meldonium is an anti-ischemic drug clinically used to treat myocardial and cerebral ischemia, which acts by shifting energy production from fatty acid oxidation to glycolysis. We investigated the effects of a 4-week meldonium pre-treatment with 300 mg/kg b.m./day of rats subjected to a well-established experimental model of renal I/R, with ischemia lasting for 45 minutes, followed by 4 hours of reperfusion. The degree of apoptosis and necrosis was evaluated by measuring renal pro-apoptotic Bax and anti-apoptotic Bcl-2 ratio, serum and kidney levels of necrotic marker - high mobility group box 1 protein (HMGB1), together with the kidney histology analysis. Our results showed that apoptotic and necrotic cell death occur simultaneously under I/R conditions, judging by the renal Bax/Bcl2 ratio rise (2.7-fold), increase in serum (22%) and renal (30%) levels of HMGB1, as well as severe tubular necrosis with dilatation of the tubular structure, cast formation, tubular lumina dilatation, brush border reduction, and loss in some renal areas cells. Meldonium pretreatment reduced the elevated Bax/Bcl2 ratio by 35%, as well as the serum and renal HMGB1 levels by 20% and notably diminished histological evidence of renal I/R necrotic injury, especially regarding tubular structures. These findings proved that meldonium protects renal cells against I/R-induced necrosis and apoptosis.",
publisher = "Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade",
journal = "Immunology at the Confluence of Multidisciplinary Approaches",
title = "Meldonium prevents acute ishemia/reperfusion inducend-renal cells death in rats",
pages = "86",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6333"
}

Đurašević, S., Stojković, M., Bogdanović, L., Grigorov, I., Bogojević, D., Jasnić, N., Vujović, P., Dakić, T., Todorović, Z.,& Đorđević, J.. (2019). Meldonium prevents acute ishemia/reperfusion inducend-renal cells death in rats. in Immunology at the Confluence of Multidisciplinary Approaches
Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade., 86.
https://hdl.handle.net/21.15107/rcub_ibiss_6333

Đurašević S, Stojković M, Bogdanović L, Grigorov I, Bogojević D, Jasnić N, Vujović P, Dakić T, Todorović Z, Đorđević J. Meldonium prevents acute ishemia/reperfusion inducend-renal cells death in rats. in Immunology at the Confluence of Multidisciplinary Approaches. 2019;:86.
https://hdl.handle.net/21.15107/rcub_ibiss_6333 .

Đurašević, Siniša, Stojković, Maja, Bogdanović, Ljiljana, Grigorov, Ilijana, Bogojević, Desanka, Jasnić, Nebojša, Vujović, Predrag, Dakić, Tamara, Todorović, Zoran, Đorđević, Jelena, "Meldonium prevents acute ishemia/reperfusion inducend-renal cells death in rats" in Immunology at the Confluence of Multidisciplinary Approaches (2019):86,
https://hdl.handle.net/21.15107/rcub_ibiss_6333 .

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 . .