Suppressive effect of interferon inducer, polyriboinosinic acid-polyribocytidylic acid on induction of uridine diphosphate-glucuronyltransferases and monooxygenases in liver microsomes of rats.
The effect of polyriboinosinic acid-polyribocytidylic acid [poly(I).poly(C)] on glucuronyltransferase activities toward 4-nitrophenol and 4-hydroxybiphenyl in liver microsomes of Wistar rats was examined by its single or co-administration with 3-methylcholanthrene and phenobarbital. The increased 4-nitrophenol glucuronyltransferase activity by treatment with 3-methylcholanthrene was significantly suppressed following the co-administration with poly(I).poly(C), although the activity was not affected by the treatment with poly(I).poly(C) alone. In addition, 4-hydroxybiphenyl glucuronyltransferase activity decreased or tended to decrease by the treatment with poly(I).poly(C) alone, and the activity induced by phenobarbital was strikingly decreased following the co-administration with poly(I).poly(C). This result suggested that poly(I).poly(C) comprehensively decrease the induction of glucuronyltransferases regardless of their multiple forms. Furthermore, contents of cytochromes P-450 and b5 were also decreased by the treatment with poly(I).poly(C) alone or the co-administration with the inducers. Concomitantly, arylhydrocarbon hydroxylase and benzphetamine N-demethylase activities were significantly decreased by the treatment alone or the co-administration with the inducers. These findings supported a view that the suppressive effect of poly(I).poly(C) may be derived from the prevention of de novo synthesis of the apoprotein of the enzymes and/or the increased degradation.
D000818:Animals; D001713:Biphenyl Compounds / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003573:Cytochrome b Group / Q000378:metabolism; D015786:Cytochromes b5; D004790:Enzyme Induction / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D066298:In Vitro Techniques; D007369:Interferon Inducers / Q000494:pharmacology*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D009596:Nitrophenols / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D001713:Biphenyl Compounds; D003573:Cytochrome b Group; D007369:Interferon Inducers; D009596:Nitrophenols; D008748:Methylcholanthrene; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; C019046:4-phenylphenol; D006899:Mixed Function Oxygenases; D006419:Heme Oxygenase (Decyclizing); D014453:Glucuronosyltransferase; D011070:Poly I-C; C024836:4-nitrophenol