Xenobiotic Metabolizing Cytocbrome P450 in Pig; a Promising Animai Model

Abstract: The pig has been used as an important animai model far 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 far humans and rodents, the data related to pig afe limited because or, among others, the presence of intra-species differences (domestic pigs and minipigs) The knowledge of the CYP superfamily in a given experimental animaI is crucial far pharmacological and toxicological tests in developing drugs and far understanding the metaboli~ pathways of toxicants and carcinogens. In addition, information on the CYP system in pigs is Important smce Il plays a domlnant role m the metabolism of veterinary drugs, whose residues rernain in the porcine tissues which afe food far humans The aim of the present review is to examine -in the liver alId extrahepatic tissues of pig -our current knowledge of the xenobioticmetabolizing CYPs be!onging lO. famili.es 1-4, in terms of drug metabolism, substrate specificity, inhibition, gene expression and receptor- dnven regulatlon, m companson wlth human data It is hoped, furthermore, that this review may stimulate research on the porcine drug-metabollzmg enzymes morder 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, animai model, xenobiotics, porcine nuclear receptors