Comparison of maturation of drug-metabolizing enzymes in calves with functioning or nonfunctioning rumen.
Drug-metabolizing enzyme activities were measured in livers from calves fed commercial milk replacer (nonfunctioning rumen [veal]), and those fed milk replacer supplemented with whole grain and hay from the first week of age (functioning rumen [ruminating calves]). After birth, cytochrome P450 and its NADPH-dependent reductase activities remained unchanged in veal calves; in ruminating calves they increased almost 50%. Cytochrome P450-mediated reactions, such as aniline hydroxylase activity, tripled in ruminating calves, but remained unchanged in veal calves. In both groups of calves, coumarin hydroxylase and 7-ethoxycoumarin 0-deethylase activities increased after birth, but maturation rates and activity values in ruminating calves were considerably greater than those of veal calves. The aminopyrine N-demethylase activity for veal calves was equal to that of calves with functioning rumen. Uridine diphosphoglucuronic acid glucuronyl transferase and glutathione-S-transferase activities also were higher in calves with functioning rumen than in veal calves. This increased activity in calves with functioning rumen probably represents a response to environmental exposure to xenobiotics. Compared with rumen-functional calves, bob veal (0 to 3 weeks old) and fancy veal (15 to 19 weeks old) calves fed commercial milk replacer have a significantly (P = 0.05) diminished capacity for metabolizing drugs and other xenobiotics. From a regulatory perspective, the variance in drug-metabolizing enzyme activities within these different market classes of calves suggests that specific studies designed to determine drug residue-depletion times in veal calves may be needed.
Kawalek
J C
JC
Pharmacology and Biochemistry Branch, Food and Drug Administration, Beltsville, MD 20705.
el Said
K R
KR
D015660:7-Alkoxycoumarin O-Dealkylase / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000704:Analysis of Variance; D000815:Aniline Hydroxylase / Q000378:metabolism; D000821:Animal Feed; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D002417:Cattle; D065637:Cytochrome P-450 CYP2A6; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D015786:Cytochromes b5 / Q000378:metabolism; D005527:Food, Fortified; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D008892:Milk; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D012417:Rumen / Q000502:physiology*
D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D000815:Aniline Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases; D065637:Cytochrome P-450 CYP2A6; D009251:NADPH-Ferrihemoprotein Reductase; D005982:Glutathione Transferase