Comparative expression of liver cytochrome P450-dependent monooxygenases in the horse and in other agricultural and laboratory species.
The apoprotein expression and the catalytic activities of cytochrome P450s involved in the biotransformation of xenobiotics were investigated in horse liver microsomes and compared with those of food producing (cattle, pigs, broiler chicks, and rabbits) and laboratory species (rats). Western blot analysis revealed the presence of proteins immunorelated to rat CYP 1A, CYP 2B, CYP 2E, and CYP 3A subfamilies in hepatic microsomes from horses and from any other examined species. With the exception of the N-demethylation of N-nitrosodimethylamine in broiler chicks, all the recorded interspecies differences were quantitative in nature. Equine preparations proved the most active in the biotransformation of the CYP 1A substrates ethoxy- and methoxyresorufin and the least active in the metabolism of aminopyrine and ethoxycoumarin. On a comparative basis, large differences were observed in the rate of the in vitro metabolism of model substrates between "minor" (rabbits, horses) and "major" food producing species. Taken in due consideration the limitations of the in vitro approach, results from this study reinforce the conclusion that studies on drug efficacy and residue depletion should be performed in each target species.
Nebbia
C
C
Department of Animal Pathology, Division of Pharmacology and Toxicology, University of Turin, Grugliasco, Italy. cnebbia@veter.unito.it
Dacasto
M
M
Rossetto Giaccherino
A
A
Giuliano Albo
A
A
Carletti
M
M
D000818:Animals; D000829:Animals, Domestic / Q000378:metabolism*; D000830:Animals, Laboratory / Q000378:metabolism*; D015153:Blotting, Western; D002417:Cattle; D002645:Chickens / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006736:Horses / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D011817:Rabbits; D051381:Rats; D013045:Species Specificity; D013552:Swine / Q000378:metabolism
D003577:Cytochrome P-450 Enzyme System