Maturational development of drug-metabolizing enzymes in dogs.
A qualitative and quantitative assessment was made of the development of hepatic drug-metabolizing enzymes (DME) in dogs as part of a study of the ability of animal test species to metabolize drugs. The following DME variables were measured in this study: amount of cytochromes P-450 and b5; activity of the NADPH and NADH-dependent reductases associated with each of these cytochromes; activity of cytochrome P-450-mediated enzymes, including aniline and coumarin hydroxylases, aminopyrine N-demethylase, and 7-ethoxycoumarin O-deethylase; activity of a uridine diphosphoglucuronic acid glucuronyl transferase with 4-methylumbelliferone as substrate; and glutathione-S-transferase activities, with dinitrochlorobenzene and dichloronitrobenzene as substrates. Most enzyme components had achieved maximal amount or activity by the fifth to eighth week after birth; they tended to decrease after weaning, although the activity of dichloronitrobenzene-glutathione transferase in geriatric dogs (312 to 525 weeks old) was approximately twofold greater than that of 8-week-old pups. There were no gender-related differences in any of the enzyme amounts or activities determined. Individual variation was pronounced even in the homogeneous colony from which these dogs were obtained.
Kawalek
J C
JC
Division of Veterinary Medical Research, Food and Drug Administration, Beltsville, MD 20705.
el Said
K R
KR
D000375:Aging / Q000378:metabolism*; D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000815:Aniline Hydroxylase / Q000378:metabolism; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003579:Cytochrome Reductases / Q000378:metabolism; D042966:Cytochrome-B(5) Reductase; D015786:Cytochromes b5 / Q000378:metabolism*; D004285:Dogs / Q000378:metabolism*; D005260:Female; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D009243:NAD / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D012737:Sex Factors; D013997:Time Factors
D009243:NAD; D009249:NADP; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D000815:Aniline Hydroxylase; D000633:Aminopyrine N-Demethylase; D009247:NADH, NADPH Oxidoreductases; D003579:Cytochrome Reductases; D042966:Cytochrome-B(5) Reductase; D009251:NADPH-Ferrihemoprotein Reductase