Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8539064 | Toxicology and Applied Pharmacology | 2018 | 10 Pages |
Abstract
It has been proved that asiatic acid (AA) directly targets mitochondria and acts as a mild mitochondrial uncoupler. In this study, we aim to investigate the protective effects of AA against ischemia/reperfusion (I/R)-induced liver injury in rats and some underlying mechanisms involved were elucidated. The results showed that 50 mg/kg AA pre-treatment significantly reduced I/R-induced liver damage, characterized by the decreased release of aspartate aminotransferase (AST) and TNF-α. Furthermore, AA pre-treatment dramatically inhibited the production of MDA and increased the hepatic SOD, catalase activities and GSH levels in liver tissue of I/R rats which indicated that AA ameliorated I/R-induced liver damage by reducing oxidative stress. In isolated liver mitochondria in I/R rats, AA improved mitochondrial respiration, decreased mitochondrial MDA level, prevented I/R-induced drop of mitochondrial membrane potential (MMP) and increased ATP content, indicating the protective effect of AA against I/R-induced mitochondrial oxidative damage. In isolated liver mitochondria from normal rats, AA was found to effectively block succinate-driven H2O2 production no matter of the presence or absence of rotenone. In addition, AA showed a clear protective effect against anoxia/reoxygenation (A/R)-induced injury in isolated rat liver mitochondria when malate/glutamate were used as respiratory substrates. After AA treatment, mitochondrial respiratory dysfunction induced by A/R was ameliorated. Also, A/R-induced mitochondrial ROS generation was significantly inhibited by AA. In conclusion, AA can attenuate I/R-induced liver damage in rats and A/R-induced mitochondrial injury in isolated rat liver mitochondria by inhibiting oxidative stress and restoring mitochondrial function. Therefore, AA might have potential as a mitochondrial protective agent for use in clinical treatment of hepatic I/R injury.
Keywords
MMPHEPESA/RRh123EGTAHepatic ischemia/reperfusion injuryRCR4-(2-hydroxyethyl)-1-piperazineethanesulfonic acidAnoxia/reoxygenationDMSOI/RROSASTAspartate aminotransferaseAsiatic acidischemia/reperfusionRETRhodamine 123reverse electron transportrespiratory control ratioMitochondrial membrane potentialReactive oxygen species
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Authors
Yapeng Lu, Huiwen Kan, Ying Wang, Dan Wang, Xueting Wang, Jing Gao, Li Zhu,