Inductive and repressive effects of rifampicin on rabbit liver microsomal cytochrome P-450.
New Zealand White rabbits were treated with rifampicin at a dose of 50 mg/kg for 4 days. The total amount of microsomal hepatic cytochrome P-450 was not modified in treated, with respect to control, animals. However, further studies involving SDS-PAGE analysis, monooxygenase activity measurements and radial immunodiffusion assays indicated that rifampicin strongly affects the level of two P-450 isoenzymes. An LM3 form was induced; this form, apparently associated with erythromycine demethylase activity and hydroxylation of progesterone preferentially in position 6 beta, was shown to be immunologically and functionally different from LM3a and LM3b. On the other hand, an LM4 form, typically induced by beta-naphthoflavone, was repressed. The concomitant inductive/repressive effect of rifampicine on two cytochrome P-450 isoenzymes makes this drug a very atypical inducer, at least in the rabbit.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D004794:Enzyme Repression / Q000187:drug effects; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000096:biosynthesis; D008862:Microsomes, Liver / Q000201:enzymology*; D011817:Rabbits; D012293:Rifampin / Q000494:pharmacology*
D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; D012293:Rifampin