[Effect of antitubercular preparations on the isoform composition of cytochrome P-450 of rat liver microsomes].
The effects of the antituberculous drugs, isoniazide, phthivazide, streptomycin and PAS, on the isoform content of rat liver microsomal cytochrome P-450 was studied by electrophoresis in acrylamide concentration gradient (5-15%) in the presence of sodium dodecyl sulphate. It was discovered that administration of the antituberculous drugs did not increase the specific content of cytochrome P-450 in rat liver microsomes. At the same time isoniazide had an inducing effect on isoforms of cytochrome P-450, with molecular weights of subunits varying within the range of 49000 to 50000 dalton. Phthivazide induced subfractions with molecular weights of subunits being equal to 50000, 49000 and 47500 dalton. PAS induced subfractions with molecular weights of subunits being equal to 54000, 50000, 49000, and 47500 dalton. Administration of streptomycin did not affect the isoform content of rat liver microsomal cytochrome P-450. For comparison purposes, a study was made of the generally recognized cytochrome P-450 inductors, phenobarbital and 3-methylcholanthrene. It is suggested that the changes in the isoform content of rat liver microsomal cytochrome P-450 might be of importance for understanding the mechanism of drug tolerance induction in the treatment of tuberculosis, since the changes discovered are likely to lead to the increased metabolic rate of the antituberculous drugs at the cytochrome P-450 level and to the accelerated excretion from the body.
D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004361:Drug Tolerance; D007536:Isomerism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D008970:Molecular Weight; D051381:Rats
D000995:Antitubercular Agents; D003577:Cytochrome P-450 Enzyme System
Vliianie protivotuberkuleznykh preparatov na izoformnyĭ sostav tsitokhroma P-450 mikrosom pecheni krys.