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The development of drug‐metabolizing enzymes in female sheep livers
Author(s) -
KADDOURI M.,
LARRIEU G.,
EECKHOUTTE C.,
GALTIER P.
Publication year - 1990
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/j.1365-2885.1990.tb00787.x
Subject(s) - ethylmorphine , benzphetamine , cytochrome , medicine , endocrinology , biology , cytochrome b5 , unspecific monooxygenase , microsome , drug metabolism , cytochrome p450 , enzyme , metabolism , biochemistry , cyp1a2
Kaddouri, M., Larrieu, G., Eeckhoutte, C. & Galtier, P. The development of drug‐metabolizing enzymes in female sheep livers. J. vet. Pharmacol. Therap. 13, 340–349. The purpose of this investigation was to determine age‐related changes of some hepatic drug‐metabolizing activities in Lacaune ewes in the foetal, neonatal (1 and 4 weeks), growing (7 months), pregnant (11 months) and adult (6 years) stages. Although microsomal cytochrome P‐450 was not detected in 3‐month‐old foetuses, it increased regularly from 1‐week‐to 11‐month‐old animals. Among mixed‐function oxidases, the development of aminopyrine and ethylmorphine N ‐demethylases, benzo(α)pyrene hydroxylase and ethoxycoumarin O ‐deethylase were correlated to that of total cytochrome P‐450. Due to their presence in foetal liver or their more rapid evolution, cytochrome b5, NADPH cytochrone c reductase, aniline hydroxylase, benzphetamine N ‐demethylase and erythromycin N ‐demethylase did not parallel the ontogenesis of cytochrome P‐450. Hepatic transferases showed different developmental patterns from mono‐oxygenases, so UDP glucuronyltransferase was detected in the foetus, reached maximum activity in all young ages up to the pregnant stage and subsequently fell in adult ewes. Concerning glutathione S‐transferase accepting l‐chloro‐2,4‐dinitrobenzene as substrate, similar values were obtained in the foetus and all young animals, whereas five‐to tenfold higher values were obtained in both pregnant and adult female sheep. N ‐acetyltransferase using sulphamethazine did not significantly change from foetuses to adults but there were large differences in the capacity of hepatic acetylation between animals belonging to the same group. P. Galtier, Laboratoire de Pharmacologie‐Toxicologie, INRA, 180 chemin de Tournefeuille, BP 3, 31931 Toulouse, France.