Abstract 201: (-)-Epigallocatechin-3-gallate inhibits the development of hepatic preneoplastic lesions in obese and hypertensive rats, a novel model of non-alcoholic steatohepatitis-related liver tumorigenesis.

Abstract Background: Non-alcoholic steatohepatitis (NASH), which involves hepatic inflammation and fibrosis, is associated with liver carcinogenesis. The activation of the renin-angiotensin system (RAS), which plays a key role in blood pressure regulation, promotes hepatic fibrogenesis. In this study, we investigated the effects of (-)-epigallocatechin-3-gallate (EGCG), a major component of green tea catechins, on the development of hepatic preneoplastic lesions in SHRSP.Z-Leprfa/IzmDmcr (SHRSP-ZF) obese and hypertensive rats. Methods: Male 7-week-old SHRSP-ZF rats and control non-obese and normotensive WKY/Izm rats were fed a high fat diet and received intraperitoneal injections of carbon tetrachloride twice a week for 8 weeks. The rats were also provided tap water containing 0.1% EGCG during the experiment. Results: SHRSP-ZF rats presented with obesity, insulin resistance, dyslipidemia, an imbalance of adipokines in the serum, and hepatic steatosis. The development of hepatic preneoplastic lesions and liver fibrosis was markedly accelerated in SHRSP-ZF rats compared to that in control rats. Additionally, in SHRSP-ZF rats, RAS was activated and inflammation and oxidative stress were induced. Administration of EGCG, however, inhibited the development of hepatic premalignant lesions by improving liver fibrosis, inhibiting RAS activation, and attenuating inflammation and oxidative stress in SHRSP-ZF rats. Conclusions: Obese and hypertensive SHRSP-ZF rats treated with a high fat diet and carbon tetrachloride displayed the histopathological and pathophysiological characteristics of NASH and developed hepatic premalignant lesions, suggesting the model might be useful for the evaluation of NASH-related liver tumorigenesis. EGCG might also be able to prevent NASH-related liver fibrosis and tumorigenesis. Citation Format: Takahiro Kochi, Masahito Shimizu, Takuji Tanaka, Hisataka Moriwaki. (-)-Epigallocatechin-3-gallate inhibits the development of hepatic preneoplastic lesions in obese and hypertensive rats, a novel model of non-alcoholic steatohepatitis-related liver tumorigenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 201. doi:10.1158/1538-7445.AM2013-201