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Characterization of Xenobiotic Biotransformation in Hepatic, Renal and Gut Tissues of Cattle and Sheep¹

Indiana University School of Medicine, Bloomington 47405 and New Mexico State University, Las Cruces 88003

⁴ To whom correspondence should be addressed.

Abstract

Microsomal and cytosolic preparations of hepatic, renal, ileal and ruminal tissues of cattle and sheep were used to measure oxidative, hydrolative and conjugative biotransformations of 11 xenobiotic substrates. Within species, enzyme activities were generally higher (P<.05) in hepatic than non-hepatic tissue but, in both species, non-hepatic tissue exhibited considerable capacities for metabolizing certain substrates. Sheep rumen wall (with papillae) was notably high in cytochrome P-450 content (34% of hepatic value), in glutathione conjugation of ethacrynic acid (223% of hepatic activity; P<.05), and UDP-glucuronidation of estrone (290% of hepatic activity; P<.05). Sheep differed (P<.05) from cattle, having lower cytochrome P-450 content in liver and ileum (but not kidney); lower N-demethylase activity in liver, but two- to threefold higher activity in kidney; lower sulfotransferase activity in liver and kidney; and higher glutathione S-transferase activity toward certain substrates. UDP-glucuronidation varied too widely among substrates to afford strong generalization in comparisons among tissues or between species. Non-hepatic tissues in ruminants exhibit considerable capacities for oxidative, hydrolative and conjugative metabolism of xenobiotics. Sheep and cattle differ widely in hepatic and non-hepatic capacities for biotransforming certain xenobiotics.

¹ Journal article 1277 of the New Mexico Agr. Exp. Sta. A preliminary report was presented at the 1984 VI Int. Symp. on Ruminant Physiol. Banff, Canada [Can. J. Anim. Sci. 64 (Suppl):278]. Authors acknowledge technical assistance by Mae Bay, Tom Dykstra, Paul Kraus and Pat Trujillo.

² Pharmacol. Sec, Med. Sci. Program, Indiana Univ. School of Med., Bloomington, IN 47405. Partial support was provided by Biomed. Res. Support Grant 5 S07 RR5371 and Pharmaceutical Manufacturer's Assoc. Foundation Research Starter Grant.

³ Dept. of Anim and Range Sci., New Mexico State Univ., Las Cruces, NM 88003. Partial support was provided by contracts DE-ACO4-76ET33626 and DEACO4-83AL21776, U.S. Dept. of Energy, Albuquerque, NM 87115.