Please use this identifier to cite or link to this item: https://biore.bio.bg.ac.rs/handle/123456789/3226
Title: The Effects of Meldonium on the Renal Acute Ischemia/Reperfusion Injury in Rats
Authors: 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
Keywords: ischemia/reperfusion;kidney;inflammation;oxidative stress;antioxidative defence;noradrenaline;lipidomics;rats
Issue Date: 15-Nov-2019
Rank: M21
Publisher: MDPI
Journal: International Journal of Molecular Sciences
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 pre-treatment protects against I/R-induced oxidative stress and apoptosis/necrosis.
URI: https://biore.bio.bg.ac.rs/handle/123456789/3226
DOI: 10.3390/ijms20225747
Appears in Collections:Journal Article

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