The effects of meldonium on the renal acute ischemia/reperfusion injury in rats
2019
Аутори:
Đurašević, SinišaStojković, Maja
Bogdanović, Ljiljana
Pavlović, Slađan
Borković Mitić, Slavica
Grigorov, Ilijana
Bogojević, Desanka
Jasnić, Nebojša
Tosti, Tomislav
Đurović, Saša
Đorđević, Jelena
Todorović, Zoran
Тип документа:
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт:
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.
Кључне речи:
Ischemia/reperfusion; Kidney; Inflammation; Oxidative stress; Antioxidative defence; Noradrenaline; Lipidomics; RatsИзвор:
International Journal of Molecular Sciences, 2019, 20, 22, 5747-Финансирање / пројекти:
- Ефекат метаболичких и неметаболичких стресора на експресију и деловање неуроендокриних регулатора енергетске хомеостазе (RS-MESTD-Basic Research (BR or ON)-173023)
- Сигнални молекули у дијабетесу: идентификација потенцијалних биолошких маркера укључених у модификацију и интеграцију сигналних путева у циљу предикције и интервенције у дијабетесу (RS-MESTD-Basic Research (BR or ON)-173020)
- Молекуларно физиолошки биомониторинг аеробних организама заснован на одређивању биохемијских биомаркера оксидационог стреса (RS-MESTD-Basic Research (BR or ON)-173041)
DOI: 10.3390/ijms20225747
ISSN: 1422-0067
PubMed: 31731785