Green tea polyphenols down-regulate inducible nitric oxide synthase (iNOS) and endothelin-1 (ET-1) proteins in carbon tetrachloride induced hepatotoxicity in vivo

Abstract

(-)-epigallocathechin gallate (EGCg) is the main and most active component of green tea polyphenols and has the strongest antioxidant effect amongst all polyphenols. The aim of present study is to investigate whether EGCg can modulate the expressions of iNOS and ET-1 protein synthesis in carbon tetrachloride (CCL4) induced hepatotoxicity in vivo. Eight-week-old ICR mice were pretreated with two doses of EGCg and then were injected with CC14 to induce hepatic necrosis. The volume fraction of necrotic liver and staining densities of iNOS and ET-I were measured using Qwin Leica image analysis. iNOS protein was also quantified by western blotting. iNOS and ET-1 were co-expressed and downregulated by EGCg in CCI4-induced degenerative and necrotic hepatocytes around the centrilobular veins in a dose- and timedependent fashion. Pretreated mice with a higher dose of EGCg showed significantly reduced necrotic liver volume and lower expression of iNOS and ET-I proteins when compared with saline control mice. We conclude that EGCg modulates the effects of CCI4-induced hepatotoxicity by down-regulating the expressions of both iNOS and ET-1 proteins. The current work is evaluating the expression of iNOS and ET-1 genes to determine whether EGCg inhibits iNOS and ET-1 gene transcription. The present study will also identify the binding activities of NF-KB and AP-1, to assess if EGCg inhibits these two DNA-binding proteins from triggering gene transcriptions of iNOS and ET-1.