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

Journal of Veterinary Medical Science

Ikuo IGARASHI³  Fumio HOSHI¹  Yoshinori SHIMAMOTO²  Hiroshi KITAMURA⁶  Mizuki SASAKI⁴  Naoaki YOKOYAMA³  Mayumi ISHIZUKA⁵  Hiromi IKADAI⁴ 

[1] Department of Small Animal Internal Medicine, School of Veterinary Medicine, Kitasato University;Department of Veterinary Teaching Hospital, School of Veterinary Medicine, Kitasato University;National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine;Department of Veterinary Parasitology, School of Veterinary Medicine, Kitasato University;Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University;Department of Comparative and Experimental Medicine, Graduate School of Medical Sciences, Nagoya City University

关键词: Babesia microti;    CYP3A;    cytochrome P450;    downregulation;    drug metabolism;   

DOI  :  10.1292/jvms.11-0036

学科分类：兽医学

来源: Japanese Society of Veterinary Science

【 摘 要 】

References(34)Cited-By(2)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.

【 授权许可】

Unknown