Inhibitory effect of rifampicin on the depressive action of interleukin-1 on cytochrome P-450-linked monooxygenase system.
It has been shown that interleukin 1 (IL-1) depresses cytochrome P-450-linked monooxygenases. In the present study, the effects of rifampicin on the depressive action of IL-1 on the activities and gene expression of xenobiotic metabolizing enzymes in liver microsomes were investigated in vivo using Wistar rats. Among the monooxygenases studied, we especially focused on the induction mechanism for CYP2D, known to be depressed by IL-1 and responsible for the oxidation of xenobiotics, debrisoquine, bufuralol, and sparteine. The CYP2D protein and its messenger RNA (mRNA) were quantitated by Western blot and slot blot hybridization analyses in the groups treated with and without rifampicin and IL-1. The results showed that the depressive action of IL-1 on CYP2D was offset by additional administration of rifampicin, and the P-450 (CYP2D-linked monooxygenase system is up-regulated at the mRNA level by rifampicin. These results show that rifampicin has a blocking effect on the depressive action of IL-1 on the CYP2D subfamily.
Third Department of Internal Medicine, Faculty of Medicine, Kagawa Medical University, Japan.
K
K
Kurokohchi
H
H
Yoneyama
M
M
Nishioka
Y
Y
Ichikawa
D015660:7-Alkoxycoumarin O-Dealkylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D015786:Cytochromes b5 / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012293:Rifampin / Q000494:pharmacology*; D013053:Spectrophotometry; D015262:Xenobiotics / Q000037:antagonists & inhibitors / Q000378:metabolism
D065690:Cytochrome P-450 CYP2D6 Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D007375:Interleukin-1; D012333:RNA, Messenger; D015262:Xenobiotics; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D019389:Cytochrome P-450 CYP2D6; C019781:benzphetamine N-demethylase; C043872:bufuralol 1'-hydroxylase; D010089:Oxidoreductases, N-Demethylating; D012293:Rifampin