OP-17 - Tea Extracts-induced Liver Injury: Lipotoxic Interaction Between Lipids and Polyphenols

Abstract

Green tea polyphenol extracts (GTE) are sold commercially as cholesterol-reducing agents and for weight reduction however, they have also been reported to be hepatotoxic. Our results from both in vitro and in vivo studies indicate that green tea polyphenols can potentiate liver injury after and during treatment with high cholesterol diet to induce experimental NASH. Eight week old male C57BL mice (n=32) were fed for 6 weeks with one of the following diets: Control diet (Con); Con +1% w/w polyphenols from green tea extract (Con+GTE); High cholesterol diet, Con+ 1% cholesterol+ 0.5% cholate w/w (HCD); HCD + 1 % polyphenols w/w (HCD+GTE). Hepatic steatosis, oxidative and inflammatory markers and bile acid synthesis pathways were measured. GTE enhanced hepatic steatosis but only in animals exposed to the high cholesterol diet. In HCD treated animals GTE elevated blood levels of liver enzymes SGOT, SGPT, and bile acids. Inflammatory and oxidative markers in the liver were also significantly increased including liver mRNA expression of TNF-alpha, IL-6, SAA1, SAA2, iNOS and levels of 4-hydroxynonenal protein adducts. The mechanism of action for GTE/cholesterol hepatotoxicity was found to be related to alteration in bile acids synthesis pathways. This study shows that liver injury in the presence of lipids could be the reason for weigh loss by high dose of polyphenols.