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In vitro cytochrome P450‐mediated hepatic activities for five substrates in specific pathogen free chickens
Author(s) -
Khalil W. F.,
Saitoh T.,
Shimoda M.,
Kokue E.
Publication year - 2001
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 - 10.1046/j.1365-2885.2001.00349.x
Subject(s) - hydroxylation , microsome , tolbutamide , cytochrome p450 , mephenytoin , biology , cyp3a , medicine , endocrinology , in vitro , cytochrome , beagle , biochemistry , chemistry , pharmacology , metabolism , enzyme , ecology , cyp2c19 , diabetes mellitus
Total hepatic microsomal cytochrome P450 (CYP) content as well as in vitro CYP mediated activities for five substrates [bufuralol 1‐hydroxylation, ethoxyresorufin O ‐deethylation, S ‐mephenytoin 4‐hydroxylation, testosterone 6β‐hydroxylation, and tolbutamide hydroxylation] were measured in specific pathogen free male Japanese leghorn chickens and male beagle dogs. The V max , K m and intrinsic clearance ( V max / K m ) for these substrates were calculated and compared between animal species in order to evaluate the drug catalytic activity in chicken liver. The total CYP content in chicken (0.296 ± 0.04 nmol/mg microsomal protein) was close to levels reported for other species including humans, cats, pigs and some nonmammalian vertebrates (e.g. snakes, frogs and trout fish), but was lower than levels measured in dogs (1.11 ± 0.22) or recorded in guinea‐pigs, hamsters, monkeys, mice, rabbits, rats, horse and ruminants. Bufuralol 1‐hydroxylation, ethoxyresorufin O ‐deethylation, S ‐mephenytoin 4‐hydroxylation, and testosterone 6β‐hydroxylation were lower in chickens than in dogs based on intrinsic clearance. On the other hand, tolbutamide hydroxylation was markedly higher in chickens than in dogs.