Expression of cytochrome P450 2A5 in a C57BL/6J mouse model of nonalcoholic fatty liver disease.

ABSTRACT

Cytochrome P450 2A5 (CYP2A5) expression is induced during the hepatotoxicity caused by various hepatotoxins and hepatitis. However, CYP2A5 expression during nonalcoholic fatty liver disease (NAFLD) is still unknown. In this study, serum biochemical parameters and liver histopathological analyses found that NAFLD had developed in C57BL/6J mice via administration of a high-fat diet continuously for 8 weeks. Subsequently, CYP2A5 expression was probed in the mice diagnosed with NAFLD that were treated with or without pyrazole, the inducer of chemical liver injury. It is shown that hepatic CYP2A5 mRNA, protein expression and coumarin 7-hydroxylase activity are enhanced with high-fat feed, and that pyrazole is able to further increase CYP2A5 expression and activity in mice with NAFLD. These results revealed that CYP2A5 is elevated during NAFLD and suggested that pyrazole and NAFLD act synergistically to induce the expression of CYP2A5 via an unclear mechanism.