Evaluation of the hepatoprotective effect of oral administration of aqueous fraction of methanolic extract of Costus afer leaves during induction of hepatocellular carcinoma with diethylnitrosamine in rats

This study evaluated the hepatoprotective effect of oral administration of aqueous fraction of methanolic extract of Costus afer leaves (CALAF) during induction of hepatocellular carcinoma (HCC) with diethylnitrosamine (DEN) in rats. The methanolic leaf extract was fractionated into hexane, ethyl acetate, butanol, and aqueous fractions. The in vitro antioxidant potential of the fractions were estimated by the assays of 2,2-diphenyl-1-picrylhydrazine and nitric oxide radical scavenging activity, ferric-reducing antioxidant potential, and total antioxidant capacity. CALAF had the most antioxidant effect. Rats were orally pretreated daily with CALAF at 100, 200, and 400 mg/kg or silymarin (hepatoprotective drug) at 50 mg/kg from 2 weeks prior to HCC induction and through 6 weeks of HCC induction. The HCC induction was by a single intraperitoneal injection of DEN at 200 mg/kg as an initiator, followed 2 weeks later by daily oral administration of 2-acetylaminofluorene at 30 mg/kg as promoter. At the end of HCC induction, levels of alpha-fetoprotein (AFP), liver function and antioxidants, gamma histone 2A family member X (γH2AX), and O6-methylguanine-DNA methyltransferase (MGMT) expressions were determined. HCC rats treated with CALAF at all doses had significantly (p < 0.05) reduced levels of AFP, aspartate aminotransferase, alanine aminotransferase, superoxide dismutase, glutathione peroxidase, reduced glutathione, and γH2AX protein expression, whereas MGMT protein expression was elevated when compared with untreated HCC rats. Thus, CALAF could be effective in protecting against DEN-induced HCC in rats by ameliorating hepatic injury and genotoxicity.