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Article

The Effects of Meldonium on the Renal Acute Ischemia/Reperfusion Injury in Rats

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Faculty of Biology, University of Belgrade, 11158 Belgrade, Serbia
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School of Medicine, University of Belgrade, 11129 Belgrade, Serbia
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Institute for Biological Research “Siniša Stanković”–National Institute of Republic of Serbia, University of Belgrade, 11060 Belgrade, Serbia
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Faculty of Chemistry, University of Belgrade, 11158 Belgrade, Serbia
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Institute of General and Physical Chemistry, University of Belgrade, 11158 Belgrade, Serbia
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University Medical Centre “Bežanijska kosa”, University of Belgrade, 11080 Belgrade, Serbia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(22), 5747; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20225747
Received: 19 October 2019 / Revised: 1 November 2019 / Accepted: 8 November 2019 / Published: 15 November 2019
(This article belongs to the Special Issue Nephrotoxicity 2019)
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 pre-treatment protects against I/R-induced oxidative stress and apoptosis/necrosis. View Full-Text
Keywords: ischemia/reperfusion; kidney; inflammation; oxidative stress; antioxidative defence; noradrenaline; lipidomics; rats ischemia/reperfusion; kidney; inflammation; oxidative stress; antioxidative defence; noradrenaline; lipidomics; rats
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MDPI and ACS Style

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. Int. J. Mol. Sci. 2019, 20, 5747. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20225747

AMA Style

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. International Journal of Molecular Sciences. 2019; 20(22):5747. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20225747

Chicago/Turabian Style

Đurašević, Siniša, Maja Stojković, Ljiljana Bogdanović, Slađan Pavlović, Slavica Borković-Mitić, Ilijana Grigorov, Desanka Bogojević, Nebojša Jasnić, Tomislav Tosti, Saša Đurović, Jelena Đorđević, and Zoran Todorović. 2019. "The Effects of Meldonium on the Renal Acute Ischemia/Reperfusion Injury in Rats" International Journal of Molecular Sciences 20, no. 22: 5747. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20225747

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