Effect of co-administration of interferon inducer, polyriboinosinic acid-polyribocytidylic acid, with SKF 525-A on hepatic drug metabolizing enzymes of rats.
The protective effect of SKF 525-A on the suppression of cytochrome P-450 content and monooxygenase activities by treatment with CoCl2 and polyriboinosinic acid-polyribocytidylic acid [poly(I.C] was compared as a part of studies of suppression of drug metabolizing enzymes by interferon inducers. Induction of heme oxygenase activity by CoCl2 and poly (I.C) was not altered by simultaneous treatment with SKF 525-A. Depression of cytochrome P-450 content and benzphetamine N-demethylase activity by treatment with CoCl2 was prevented by co-treatment with SKF 525-A. This effect was explained by the prevention of release of heme from cytochrome P-450 by forming metabolic intermediate complexes with metabolites of SKF 525-A. On the other hand, poly(I.C) significantly suppressed P-450 content and benzphetamine N-demethylase and benzo [a] pyrene hydroxylase activities, even under simultaneous treatment with SKF 525-A. This inhibition by poly (I.C) was accompanied by weak staining of proteins corresponding to cytochrome P-450 in SDS gel electrophoresis. In addition, the activity of non-heme enzyme, 4-hydroxybiphenyl glucuronyltransferase, was suppressed by treatment with poly (I.C) but not by CoCl2-treatment. These findings strongly suggested that, unlike CoCl2, poly (I.C) suppressed cytochrome P-450 content and monooxygenase activities due to decreased synthesis or increased degradation of the apoprotein of cytochrome P-450 with slight contribution of the induced heme oxygenase.
D000818:Animals; D001579:Benzopyrene Hydroxylase / Q000032:analysis; D003035:Cobalt / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis*; D004591:Electrophoresis, Polyacrylamide Gel; D014453:Glucuronosyltransferase / Q000032:analysis; D006419:Heme Oxygenase (Decyclizing) / Q000032:analysis; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D011070:Poly I-C / Q000008:administration & dosage / Q000494:pharmacology*; D011335:Proadifen / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D003035:Cobalt; D003577:Cytochrome P-450 Enzyme System; D011335:Proadifen; D001579:Benzopyrene Hydroxylase; D006419:Heme Oxygenase (Decyclizing); D014453:Glucuronosyltransferase; C018021:cobaltous chloride; D011070:Poly I-C