Downregulation of Hepatic Cytochrome P450 3A in Mice Infected with Babesia microti

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  • SHIMAMOTO Yoshinori
    Department of Veterinary Teaching Hospital, School of Veterinary Medicine, Kitasato University
  • SASAKI Mizuki
    Department of Veterinary Parasitology, School of Veterinary Medicine, Kitasato University
  • IKADAI Hiromi
    Department of Veterinary Parasitology, School of Veterinary Medicine, Kitasato University
  • ISHIZUKA Mayumi
    Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University
  • YOKOYAMA Naoaki
    National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine
  • IGARASHI Ikuo
    National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine
  • HOSHI Fumio
    Department of Small Animal Internal Medicine, School of Veterinary Medicine, Kitasato University
  • KITAMURA Hiroshi
    Department of Comparative and Experimental Medicine, Graduate School of Medical Sciences, Nagoya City University

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Abstract

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.<br>

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