title: Downregulation of hepatic cytochrome P450 3A in mice infected with Babesia microti.
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.
authors.affiliation: Department of Veterinary Teaching Hospital, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034–8628, Japan. shimamot@vmas.kitasato-u.ac.jp
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Shimamoto
authors.forename: Mizuki
authors.initials: M
authors.lastname: Sasaki
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ikadai
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ishizuka
authors.forename: Naoaki
authors.initials: N
authors.lastname: Yokoyama
authors.forename: Ikuo
authors.initials: I
authors.lastname: Igarashi
authors.forename: Fumio
authors.initials: F
authors.lastname: Hoshi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitamura
mesh_terms: D000818:Animals; D041001:Babesia microti / Q000302:isolation & purification*; D001404:Babesiosis / Q000201:enzymology* / Q000469:parasitology; D015153:Blotting, Western; D051544:Cytochrome P-450 CYP3A / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051544:Cytochrome P-450 CYP3A