Biotransformation enzymes as determinants of xenobiotic toxicity in domestic animals

After coming in contact with living organisms, the majority of foreign compounds undergo a number of chemical reactions known as biotransformations. These are performed by hepatic and extra-hepatic enzyme systems and usually yield more polar derivatives, referred to as ‘metabolites’, which may leave the body via the urinary and biliary routes or be excreted in animal products such as milk and eggs. Biotransformation does not always imply detoxification because in certain instances metabolites will be produced that are capable of reacting with tissue macromolecules or acquiring toxic properties different to or greater than those of the parent molecule. In this review, which is focused on domestic animals, the role played by oxidative, reductive, hydrolytic and conjugative biotransformation enzymes in the activation/detoxification of xenobiotics is examined. The relationship between extra-hepatic metabolism and target organ toxicity as well as the action of rumen microflora on feed additives, phytotoxins, and pesticides are then discussed. Some of the most important metabolic-based species-related susceptibilities to different poisons, and the influence of enzyme inducers or inhibitors on xenobiotic toxicity and drug safety are also reviewed.