Vet. Res. 36 (2005) 179-190
DOI: 10.1051/vetres:2004066

Effect of breed and gender on bovine liver cytochrome P450 3A (CYP3A) expression and inter-species comparison with other domestic ruminants

Mauro Dacasto^a, Claudine Eeckhoutte^b, Francesca Capolongoa^a, Jacques Dupuy^b, Monica Carletti^c, Cécile Calléja^b, Carlo Nebbia^c, Michel Alvinerie^b and Pierre Galtier<sup>b

a</sup>  Dipartimento di Sanità Pubblica, Patologia Comparata ed Igiene Veterinaria, Area di Farmacologia e Tossicologia, Università di Padova, 35020 Agripolis Legnaro (Padova), Italia
^b  Institut National de la Recherche Agronomique, UR66, Laboratoire de Pharmacologie-Toxicologie, 31931 Toulouse, France
^c  Dipartimento di Patologia Animale, sezione di Farmacologia e Tossicologia, Università di Torino, 10095 Grugliasco (Torino), Italia

(Received 17 June 2004; accepted 8 October 2004)

Abstract - The cytochrome P450 (P450) superfamily represents a group of relevant enzymes in the field of drug metabolism and several exogenous or constitutional factors contribute to regulate its expression. Cattle represent an important source of animal-derived food-products and studies concerning the P450 expression are needed for the extrapolation of pharmacotoxicological data from one species to another and for the evaluation of the consumer's risk associated with the consumption of harmful residues found in foodstuffs. In the present study, possible breed-, gender- and species-differences in P4503A (the P450 subfamily more expressed in the human liver) expression were studied in vitro in Piedmontese (PDM) and Limousin (LIM) meat cattle breeds of both sexes and in domestic Ruminants (cattle, sheep and goats). Cytochrome P450 and P4503A contents as well as CYP3A-dependent drug metabolising enzymes (DME) were measured in liver microsomes. Significant lower levels of P450 (P < 0.001) and P4503A (P < 0.05) contents were observed in PDM vs. LIM of both sexes; the P4503A-dependent DME activities were significantly (P values ranging from 0.05 up to 0.001) higher in PDM cattle, particularly in males. A gender-effect in DME activities was noticed (P < 0.05) only in PDM male cattle. With regards to the species, the expression of both P4503A apoprotein and some of the related DME activities were more pronounced in sheep (P < 0.01 vs. cattle) and in goats (P < 0.05 vs. sheep; P < 0.01 vs. cattle) than in cattle. The significant differences in P4503A expression observed in LIM and PDM cattle are consistent with previously published data on strain- and breed-differences pointed out in rats and men. As far as a possible sex-effect is concerned, no clear-cut evidence is likely to be drawn. Finally, P4503A expression was more relevant in small ruminants.

Key words: ruminants / liver drug metabolism / CYP3A / gender / breed

Corresponding author: Mauro Dacasto mauro.dacasto@unipd.it

© INRA, EDP Sciences 2005