Downregulation of hepatic cytochrome P450 3A in mice infected with Babesia microti.

To investigate effects of Babesia infection on drug metabolism, we intraperitoneally inoculated B. microti into ICR mice and measured the expression and activity of hepatic cytochrome P450 (CYP) 3A, a major drug-metabolizing enzyme. Twelve days after infection, CYP3A11 mRNA, CYP3A protein and activity and mRNAs of nuclear receptors, which participate in CYP3A expression, were significantly reduced. These results suggest that B. microti infection suppresses CYP3A-dependent drug metabolism. Additionally, tumor necrosis factor (TNF)-α and nitric oxide synthase (NOS) 2 mRNAs were induced in the infected mouse liver. Since TNF-α is one of the potent mediators that induce NOS2 and repress CYP3A transcription, the possible involvement of TNF-α in this downregulation of CYP3A was discussed.