Asiatic acid ameliorates hepatic ischemia/reperfusion injury in rats via mitochondria-targeted protective mechanism

Toxicol Appl Pharmacol. 2018 Jan 1:338:214-223. doi: 10.1016/j.taap.2017.11.023. Epub 2017 Nov 28.

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 50mg/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: Asiatic acid; Hepatic ischemia/reperfusion injury; Mitochondrial anoxia/reoxygenation; Reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Liver / blood supply*
  • Male
  • Malondialdehyde / analysis
  • Mitochondria, Liver / drug effects*
  • Pentacyclic Triterpenes / pharmacology*
  • Pentacyclic Triterpenes / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Reperfusion Injury / drug therapy*

Substances

  • Pentacyclic Triterpenes
  • Reactive Oxygen Species
  • Malondialdehyde
  • asiatic acid