Comparison of maturation of drug-metabolizing enzymes in calves with functioning or nonfunctioning rumen

Joseph C. Kawalek From the Pharmacology and Biochemistry Branch, Division of Animal Research, Office of Science - Beltsville, Center for Veterinary Medicine, Food and Drug Administration, Agricultural Research Center - East, Bldg 328A, Center Road, Beltsville, MD 20705 (Kawalek); and Gulf Coast Seafood Laboratory Branch, Division of Science and Applied Technology, Office of Seafood, Center for Food Safety and Nutrition, Food and Drug Administration, PO Box 158, Dauphin Island, AL 36528 (El Said).

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Kathleen R. El Said From the Pharmacology and Biochemistry Branch, Division of Animal Research, Office of Science - Beltsville, Center for Veterinary Medicine, Food and Drug Administration, Agricultural Research Center - East, Bldg 328A, Center Road, Beltsville, MD 20705 (Kawalek); and Gulf Coast Seafood Laboratory Branch, Division of Science and Applied Technology, Office of Seafood, Center for Food Safety and Nutrition, Food and Drug Administration, PO Box 158, Dauphin Island, AL 36528 (El Said).

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Summary

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.

Summary

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.

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