Received for publication September 27, 2007.
Revised February 6, 2008.
Accepted for publication February 6, 2008.

Effect of breed upon cytochrome P450s and phase II enzymes expression in cattle liver

Abstract

Cattle represent an important source of animal-derived food-products; nonetheless, our knowledge about the expression of drug metabolizing enzymes (DMEs) in present and other food-producing animals still remains superficial, despite the obvious toxicological consequences. Breed represents an internal factor which modulates DMEs expression and catalytic activity. In the present work, the effect of breed upon relevant phase I and II DMEs was investigated at the pre-transcriptional and post-translational levels in male Charolais (CH), Piedmontese (PM) and Blonde d'Aquitaine (BA) cattle. As specific substrates for cattle have not yet been identified, the breed effect upon specific cytochrome P450s (CYPs), glucuronyl or glutathione transferase (UGT and GST, respectively) DMEs, in terms of catalytic activity, was determined by using human marker substrates. Among CYPs, benzphetamine N-demethylase, 16-, 6- and 2-testosterone hydroxylase, aniline and p-nitrophenol hydroxylase, -naphthol and p-nitrophenol UGT activities were significantly higher in CH; by contrast, lower levels of CYP1A1- and CYP1A2-like, CYP2B6-like, CYP2C9- and CYP2C18-like, CYP3A4-like, and UGT1A1-like mRNAs were noticed, with CH<PMBA as a trend. Cytochrome P450 2B and CYP3A mRNA results were confirmed with immunoblotting, too. As regards conjugative DMEs, UGT1A6-like mRNA levels were consistent with respective catalytic activities. Both 1-chloro-2,4-dinitrobenzene and 3,4- dichloronitrobenzene GST activities were higher in BA, and these results agreed with GSTA1-, GSTM1- and GSTP1-like mRNA amounts. Correlation analysis between catalytic activities and mRNAs showed either significant or uneven results, depending on the substrate. These findings confirm previous data obtained in laboratory species; however, further studies are required to ascribe this behaviour to pre-transcriptional or post-translational phenomena.

Key words: CYP1A, CYP2B, CYP2C, CYP2E, CYP3A, cytochrome P450 catalyzed oxidations, glutathione transferases, phase II drug metabolism, UDP glucuronyltransferases