(-)-Epigallocatechin-3-gallate suppresses hepatic preneoplastic lesions developed in a novel rat model of non-alcoholic steatohepatitis

PURPOSE: Non-alcoholic fatty liver disease (NAFLD) ranges from simple steatosis to non-alcoholic steatohepatitis (NASH). NASH, which is accompanied by increased oxidative stress and inflammation in the liver, is associated with hepatic carcinogenesis. Green tea catechins (GTCs) possess anti-oxidant, anti-inflammatory, and cancer-preventive properties. In this study, we investigated whether (-)-epigallocatechin-3-gallate (EGCG), a major component of GTCs, inhibits NAFLD/NASH-related liver tumorigenesis. METHODS: Male 8-week-old Sprague–Dawley (SD) rats were administered a single intraperitoneal injection of a hepatic carcinogen diethylnitrosamine (DEN, 30 mg/kg body weight) and then fed a high-fat diet (HFD) for 7 weeks. The rats were also provided tap water containing 0.01% or 0.1% EGCG during the experiment. RESULTS: At sacrifice, the livers of SD rats treated with DEN and HFD exhibited marked development of glutathione S-transferase placental form (GST-P)-positive foci, a hepatic preneoplastic lesion, and this was associated with hepatic steatosis, oxidative stress and inflammation, and hepatocyte proliferation. EGCG administration, however, inhibited the development of GST-P-positive foci by decreasing hepatic triglyceride content, reducing hepatic fibrosis, lowering oxidative stress, attenuating inflammation, and inhibiting excessive hepatocyte proliferation in DEN- and HFD-treated SD rats. These findings suggest that the experimental model of SD rats treated with HFD and DEN, in which histopathological and pathophysiological characteristics of NASH and the development of hepatic premalignant lesions were observed, might facilitate the evaluation of liver tumorigenesis associated with NAFLD/NASH. CONCLUSIONS: Administering EGCG, a GTC, might serve as an effective chemoprevention modality for NAFLD/NASH-related liver tumorigenesis.