The effects of meldonium on the renal acute ischemia/reperfusion injury in rats
Autori
Đurašević, SinišaStojković, Maja
Bogdanović, Ljiljana
Pavlović, Slađan Z.
Borković-Mitić, Slavica S.
Grigorov, Ilijana
Bogojević, Desanka
Jasnić, Nebojša
Tosti, Tomislav
Đurović, Saša
Popović-Đorđević, Jelena
Todorović, Zoran B.
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
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 th...e 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.
Ključne reči:
Antioxidative defence / Inflammation / Ischemia/reperfusion / Kidney / Lipidomics / Noradrenaline / Oxidative stress / RatsIzvor:
International Journal of Molecular Sciences, 2019, 20, 22Izdavač:
- MDPI
Finansiranje / projekti:
- Efekat metaboličkih i nemetaboličkih stresora na ekspresiju i delovanje neuroendokrinih regulatora energetske homeostaze (RS-MESTD-Basic Research (BR or ON)-173023)
- Signalni molekuli u dijabetesu: identifikacija potencijalnih bioloških markera uključenih u modifikaciju i integraciju signalnih puteva u cilju predikcije i intervencije u dijabetesu (RS-MESTD-Basic Research (BR or ON)-173020)
- Molekularno fiziološki biomonitoring aerobnih organizama zasnovan na određivanju biohemijskih biomarkera oksidacionog stresa (RS-MESTD-Basic Research (BR or ON)-173041)
DOI: 10.3390/ijms20225747
ISSN: 1422-0067
WoS: 000502786800229
Scopus: 2-s2.0-85075040523
Kolekcije
Institucija/grupa
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Đurašević, Siniša AU - Stojković, Maja AU - Bogdanović, Ljiljana AU - Pavlović, Slađan Z. AU - Borković-Mitić, Slavica S. AU - Grigorov, Ilijana AU - Bogojević, Desanka AU - Jasnić, Nebojša AU - Tosti, Tomislav AU - Đurović, Saša AU - Popović-Đorđević, Jelena AU - Todorović, Zoran B. PY - 2019 UR - https://cherry.chem.bg.ac.rs/handle/123456789/3767 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 VL - 20 IS - 22 DO - 10.3390/ijms20225747 ER -
@article{ author = "Đurašević, Siniša and Stojković, Maja and Bogdanović, Ljiljana and Pavlović, Slađan Z. and Borković-Mitić, Slavica S. and Grigorov, Ilijana and Bogojević, Desanka and Jasnić, Nebojša and Tosti, Tomislav and Đurović, Saša and Popović-Đorđević, Jelena and Todorović, Zoran B.", 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", volume = "20", number = "22", doi = "10.3390/ijms20225747" }
Đurašević, S., Stojković, M., Bogdanović, L., Pavlović, S. Z., Borković-Mitić, S. S., Grigorov, I., Bogojević, D., Jasnić, N., Tosti, T., Đurović, S., Popović-Đorđević, J.,& Todorović, Z. B.. (2019). The effects of meldonium on the renal acute ischemia/reperfusion injury in rats. in International Journal of Molecular Sciences MDPI., 20(22). https://doi.org/10.3390/ijms20225747
Đurašević S, Stojković M, Bogdanović L, Pavlović SZ, Borković-Mitić SS, Grigorov I, Bogojević D, Jasnić N, Tosti T, Đurović S, Popović-Đorđević J, Todorović ZB. The effects of meldonium on the renal acute ischemia/reperfusion injury in rats. in International Journal of Molecular Sciences. 2019;20(22). doi:10.3390/ijms20225747 .
Đurašević, Siniša, Stojković, Maja, Bogdanović, Ljiljana, Pavlović, Slađan Z., Borković-Mitić, Slavica S., Grigorov, Ilijana, Bogojević, Desanka, Jasnić, Nebojša, Tosti, Tomislav, Đurović, Saša, Popović-Đorđević, Jelena, Todorović, Zoran B., "The effects of meldonium on the renal acute ischemia/reperfusion injury in rats" in International Journal of Molecular Sciences, 20, no. 22 (2019), https://doi.org/10.3390/ijms20225747 . .