Ameliorative effect of silibinin against N-nitrosodimethylamine-induced hepatic fibrosis in rats.

The protective effect of silibinin (SBN) against hepatic fibrosis induced by repeated intermittent administration of N-nitrosodimethylamine (DMN) was investigated in rats. Oral administration of SBN recovered body and liver weight loss and reversed the elevation of serum AST, ALT and ALP accompanied by their fall in the liver tissue in DMN-induced fibrotic rats. Severe oxidative stress induced in fibrotic rats was evidenced by two to three fold elevation in MDA and protein carbonyl levels associated with a fall in the activities of SOD and CAT in repeated DMN treatment and this adversity was protected by SBN post-treatment. Further, the fall in the activities of ATPases and increase in the levels of hydroxyproline and collagen observed in the liver tissue of DMN treated rats was prevented and reversed back toward normalcy by SBN post-treatment. Recovery of rat liver tissue against DMN-induced hepatocellular necrosis, inflammatory changes and hepatic fibrosis by SBN treatment is also confirmed by both H & E and Masson's trichrome stained histopathological evaluation of liver tissue. In conclusion, SBN exhibit hepatoprotective, antioxidant, free radical scavenging, membrane stabilizing and anti-fibrotic activity against DMN-induced hepatic fibrosis suggesting that it may be useful as a therapeutic agent toward amelioration of hepatic fibrosis.