Effects of the interferon inducing agents tilorone and polyriboinosinic acid . polyribocytidylic acid (poly IC) on the hepatic monooxygenase systems of the developing neonatal rat.
This paper describes the effects of the interferon inducing agents tilorone and polyriboinosinic acid . polyribocytidylic acid (poly IC) on the postnatal development of hepatic cytochrome P-450-linked monooxygenase systems of male rats from birth through early adolescence. The administration of tilorone to rats on days 1 and 2 postpartum modified the changes in the activities of hepatic monooxygenase systems that occur normally during the first four days postpartum. Thus, aniline hydroxylase activity, which develops very rapidly during the first 2 days postpartum, was depressed markedly by tilorone, ethylmorphine N-demethylase activity was depressed moderately, and benzo[a] pyrene hydroxylase, normally the slowest of the three monooxygenase activities to develop, was induced. These changes in monooxygenase activities occurred without a significant change in the cytochrome P-450 content. These observations suggest that not all species of neonatal cytochrome P-450 are affected equally by tilorone administration. By day 7 postpartum, the cytochrome P-450 content and all three monooxygenase activities were depressed in rats that had received tilorone on days 1 and 2 postpartum. All three monooxygenase systems were depressed by the administration of a single dose of poly IC (10 mg/kg) in 1-, 2-, 21-, 28- and 56-day-old rats. The length of the period between maximal depression and complete recovery of cytochrome P-450 systems was shown to be a function of the age of the rat; it increased from about 6 hr in 1-day-old rats to 48 hr in 56-day-old rats. Protein is synthesized more rapidly and degraded more slowly in neonate than in adult animals; this may account for the more rapid recovery of poly IC-induced depression of monooxygenase systems in neonates.
D000375:Aging; D000815:Aniline Hydroxylase / Q000037:antagonists & inhibitors; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001579:Benzopyrene Hydroxylase / Q000037:antagonists & inhibitors; D003577:Cytochrome P-450 Enzyme System; D004790:Enzyme Induction / Q000187:drug effects; D005037:Ethylmorphine-N-Demethylase / Q000037:antagonists & inhibitors; D005449:Fluorenes / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010105:Oxygenases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011070:Poly I-C / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013994:Tilorone / Q000494:pharmacology*
D005449:Fluorenes; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D000815:Aniline Hydroxylase; D001579:Benzopyrene Hydroxylase; D005037:Ethylmorphine-N-Demethylase; D013994:Tilorone; D011070:Poly I-C