-lipoic acid protects against carbon tetrachloride-induced liver cirrhosis through the suppression of the TGF-/Smad3 pathway and autophagy

摘要

-lipoic acid (ALA) is a naturally occurring antioxidant with protective effects against various hepatic injuries. The aim of the present study was to investigate the mechanisms by which ALA protects the liver from carbon tetrachloride (CCl4)-induced liver cirrhosis. The widely used liver cirrhosis rat model was established via an intraperitoneal injection of 2 mg/kg 50% CCl4, three times/week for 8 weeks. Simultaneously, 50 or 100 mg/kg ALA was orally administrated to the rats every day for 8 weeks. The activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was detected in the serum. The pathological liver injuries were analyzed using hematoxylin and eosin and Masson's trichrome staining. The principal factors involved in the transforming growth factor- (TGF-)/mothers against decapentaplegic homolog 9 (Smad3) and protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathways and in autophagy were examined using reverse transcription-quantitative polymerase chain reaction or western blot analysis. The results demonstrated that the administration of ALA alleviated CCl4-induced liver injury, as demonstrated by decreased ALT and AST activity, improved pathological injuries and reduced collagen deposition. The CCl4-induced increase in TGF- and phosphorylated-Smad3 expression levels was additionally inhibited by treatment with ALA. Furthermore, the administration of ALA reversed the CCl4-induced upregulation of light chain 3II and Beclin-1, and downregulation of p62. The CCl4-induced suppression of the AKT/mTOR pathway was additionally restored following treatment with ALA. In combination, the results of the present study demonstrated that ALA was able to protect CCl4-induced liver cirrhosis, an effect that may be associated with inactivation of the TGF-/Smad3 pathway and suppression of autophagy.