Effect of diosmin on apoptotic signaling molecules in N-nitrosodiethylamine-induced hepatocellular carcinoma in experimental rats

The aim of the present study was to evaluate the antioxidant and chemopreventive efficiency of diosmin against N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis in adult male rats. Rats were classified into four groups as follows: Group I: Control, Group II: NDEA-induced hepatocellular carcinogenic rats, Group III: Cancer-bearing animals treated with diosmin (200 mg/kg/body weight/day) orally for 28 days, Group IV: Control animals treated with diosmin (200 mg/kg/body weight/day) alone for 28 days. The model of NDEA-induced HCC rats elicited significant increases in alpha-fetoprotein (AFP), lipid peroxidation (LPO) and increase in anti-apoptotic proteins (Bcl-2, Bcl-xL and Mcl-1) with a concomitant significant decline in liver antioxidant enzymes, pro-apoptotic (Bax and Bad) and caspase-3 &-9 proteins. The oral administration of diosmin as a protective agent normalized the altered levels of AFP, LPO, antioxidant enzymes, pro- and anti-apoptotic proteins as well as caspase-3 and -9 proteins. Transmission electron microscopical studies also revealed that treatment of diosmin has a perspective anti-cancer activity by rearranging hepatic cell structure and its integrity. Results of this study suggest that diosmin may be one of a pharmacological and therapeutic representative against hepatocellular carcinoma.