In vitro cytochrome P450-mediated hepatic activities for five substrates in specific pathogen free chickens.
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 6beta-hydroxylation, and tolbutamide hydroxylation] were measured in specific pathogen free male Japanese leghorn chickens and male beagle dogs. The Vmax, Km and intrinsic clearance (Vmax/Km) 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 6beta-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.
Khalil
W F
WF
Department of Veterinary Medicine, Tokyo University of Agriculture and Technology, Fuchu, Tokyo183-8509, Japan.
Saitoh
T
T
Shimoda
M
M
Kokue
E
E
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D001682:Biological Availability; D001711:Biotransformation; D002645:Chickens; D019363:Cytochrome P-450 CYP1A1 / Q000493:pharmacokinetics; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism / Q000493:pharmacokinetics* / Q000502:physiology; D004285:Dogs; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008862:Microsomes, Liver / Q000201:enzymology* / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000493:pharmacokinetics; D013045:Species Specificity; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000493:pharmacokinetics; D013379:Substrate Specificity
D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D051544:Cytochrome P-450 CYP3A; D039181:Steroid 16-alpha-Hydroxylase; D010089:Oxidoreductases, N-Demethylating