Expressional repression of hepatic cytochrome P450 2d in ICR mice infected with Babesia microti

Abstract

We previously reported that Babesia microti infection repressed expression and activity of hepatic drug metabolizing enzyme cytochrome P450 (Cyp) 3a in ICR mice (J. Vet. Med. Sci. 2011, in press). The purpose of this study is to investigate effects of B. microti infection on Cyp2d, another major isoform in the mouse liver. Twelve days after the infection, we observed decrease of transcripts for hepatocyte nuclear factor (HNF)‐4, which is responsible for Cyp2d expression. In agreement, Cyp2d9 mRNA and protein were clearly decreased on 12 days. Moreover, bunitrolol metabolism assay indicates Cyp2d activity was also repressed on 12 days. Babesia infection induced mRNAs of hepatic TNF‐α and NOS2, both of which are supposed to regulate Cyp expression in the liver. Collectively, Babesia decreased Cyp2d‐dependent metabolism in mice possibly by activation of the TNF‐α‐NOS2 axis.