High CYP2E1 activity correlates with hepatofibrogenesis induced by nitrosamines.

High CYP2E1 activity correlates with hepatofibrogenesis induced by nitrosamines. Oncotarget. 2017 Dec 22;8(68):112199-112210 Authors: Gao J, Wang GJ, Wang Z, Gao N, Li J, Zhang YF, Zhou J, Zhang HX, Wen Q, Jin H, Qiao HL Abstract Hepatofibrosis, which leads to cirrhosis and eventual hepatocellular carcinoma, is a common response to chronic toxin-mediated liver injury. Nitrosamines are potent hepatotoxic agents that cause necrosis and subsequent fibrosis in the liver as a result of cytochrome P450 2E1 (CYP2E1)-dependent metabolism, which generates toxic metabolites that form adducts with nucleic acids, leading to hepatotoxicity and mutagenesis. Herein, CYP2E1 activity and content were determined in fibrotic liver tissue from patients with hepatocellular carcinoma. The relationship between CYP2E1 innate activity and hepatofibrogenesis was evaluated, the effect of inhibition of CYP2E1 activity on hepatofibrosis was determined in a Sprague-Dawley rat model of diethylnitrosamine-induced hepatofibrosis. The results demonstrated that the CYP2E1 activities in human fibrotic tissues are significantly higher than that in normal liver tissues. In rats treated with diethylnitrosamine, the livers demonstrated various degree of fibrotic changes and collagen deposition in individual rats. The Ishak score, which determines the stage of fibrosis, correlated with CYP2E1 innate activity, with greater fibrosis in rat livers with higher CYP2E1 innate act...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research