Repression of Hepatic Cytochrome P450 2D Expression in Mice during Babesia microti infection.
Shimamoto Y1, Watanabe K, Ikadai H, Okamura M, Ishizuka M.
Abstract
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.
PMID: 24784440 [PubMed - as supplied by publisher] Free full text
Quote - The results of this study demonstrated the repression of CYP2Dexpression during anemia resulting from Babesia infection. The decline in CYP2D-dependent metabolism can lead to an increase in the concentration of substrate drugs, such as antihypertensive agents and antidepressants, in the blood leading to an increase in the incidence of adverse drug reactions. Therefore, careful selection of drug dosage is needed in the treatment of hypertensive or depressive patients with babesiosis. - End Quote
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