Xenobiotic Metabolizing Cytochrome P450 in Pig, a Promising Animal Model

Emanuela      Puccinelli; Pier      Giovanni Gervasi; Vincenzo      Longo

Abstract

The pig has been used as an important animal model for human studies because of its similarity in size, physiology and disease development. However, in contrast to the extensive data available on the cytochrome P450 (CYP) system for humans and rodents, the data related to pig are limited because of, among others, the presence of intra-species differences (domestic pigs and minipigs). The knowledge of the CYP superfamily in a given experimental animal is crucial for pharmacological and toxicological tests in developing drugs and for understanding the metabolic pathways of toxicants and carcinogens. In addition, information on the CYP system in pigs is important since it plays a dominant role in the metabolism of veterinary drugs, whose residues remain in the porcine tissues which are food for humans.

The aim of the present review is to examine - in the liver and extrahepatic tissues of pig - our current knowledge of the xenobioticmetabolizing CYPs belonging to families 1-4, in terms of drug metabolism, substrate specificity, inhibition, gene expression and receptor- driven regulation, in comparison with human data. It is hoped, furthermore, that this review may stimulate research on the porcine drug – metabolizing enzymes in order to evaluate the hypothesis whereby pig data may better reflect human drug metabolism and toxicity than those obtained from the traditional non-rodent models.

Keywords: Pig, minipig, cytochrome P450 (CYP), liver, extrahepatic tissues, animal model, xenobiotics, porcine nuclear receptors, carcinogens, hypercholesterolemia