Repression of hepatic cytochrome P450 2D expression in mice during Babesia microti infection.
To examine the effect of Babesia infection on the level of the drug-metabolizing enzyme hepatic cytochrome P450 (CYP) 2D, we intraperitoneally inoculated Babesia microti into male ICR mice. CYP2D protein and CYP2D9 mRNA were significantly decreased at 12 days after infection with B. microti. The activity of bunitrolol 4-hydroxylase, which is catalyzed by CYP2D, was also significantly decreased. The mRNA levels of transcriptional regulators of CYP2D9, hepatocyte nuclear factor 4α and signal transducer and activator of transcription 5b, were markedly suppressed. These results suggest that Babesia infection represses CYP2D expression in the mouse liver. The decline in CYP2D-dependent drug metabolism might be involved in the incidence of adverse drug reactions in patients with babesiosis.
Department of Veterinary Teaching Hospital, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, Japan.
Yoshinori
Y
Shimamoto
Kensuke
K
Watanabe
Hiromi
H
Ikadai
Masashi
M
Okamura
Mayumi
M
Ishizuka
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D041001:Babesia microti; D001404:Babesiosis / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D051557:Hepatocyte Nuclear Factor 4; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008954:Models, Biological; D060888:Real-Time Polymerase Chain Reaction; D050799:STAT5 Transcription Factor / Q000378:metabolism
D017931:DNA Primers; D051557:Hepatocyte Nuclear Factor 4; D050799:STAT5 Transcription Factor; C494096:Stat5b protein, mouse; D001189:Aryl Hydrocarbon Hydroxylases