Cytochrome P450 Expression in the Liver of Food-Producing Animals

Abstract

A number of enzyme systems participate in the metabolism of chemicals, but undoubtedly the most important are the cytochromes P450 (CYP). It is a versatile enzyme system, capable of metabolising structurally diverse chemicals. To achieve this broad substrate specificity it exists as a superfamily of enzymes, each family being characterised by different substrate specificity; families CYP1, CYP2 and CYP3 are responsible for the metabolism of exogenous chemicals. Although our current knowledge of the expression and function of cytochromes P450 in humans and laboratory animals is extensive, little is known about this enzyme system in food-producing animals, despite its dominant role in the metabolism of veterinary drugs, and the crucial role it plays in controlling the levels of drug and other chemical residues in edible tissues and food products that humans consume, a matter of major current concern. Most studies dealing with the expression of cytochromes P450 in food-producing animals utilised substrate probes defined in rats and humans and/or antibodies raised to rat or human antigens. Such an approach can prove misleading as it assumes that orthologue proteins in other animals share the same substrate specificity and, moreover, although antibodies raised to human or rat antigens may recognise epitopes in other species, they do not constitute unequivocal proof that the detected proteins are structurally identical. Despite these drawbacks, there is substantial experimental evidence that CYP1, CYP2 and CYP3 families are expressed in food-producing animals, but their role in the metabolism of veterinary drugs and other xenobiotics has not been addressed.

High expression of the mRNA of cytochrome P450 and phase II enzymes in the lung and kidney tissues of cattle

“…CYP1A2, which is involved in the metabolism of caffeine and heterocyclic amines (Ioannides,200), was expressed mainly in the liver. Unlike the results with CYP1A1, the CYP1A2 results agree with those reported in rats and humans (Ioannides, 2006). The induction of CYP1A mRNAs in the different tissues of cattle is mainly mediated though the binding of xenobiotics to a cytosolic aryl hydrocarbon receptor (AhR).…”

“…These enzymes metabolize a wide range of endogenous and exogenous xenobiotic compounds, resulting in either the activation or detoxification of the xenobiotics, depending on the enzyme involved (Ioannides, 2006). Thus, the response of the body to physiological substrates, therapeutic drugs, carcinogens and other toxicants and pollutants can be greatly influenced by the differential expression of CYP enzymes in different tissues (Guengerich, 1997).…”

“…Most studies have used rats and humans as the reference species, simply because they have been extensively studied and antibodies are commercially available. However, extrapolation of data obtained using rat or human probes or antibodies with the tissues of food-producing animals, such as cattle, remains a difficult task because of the well-established species differences in the activity, expression and regulation of CYP proteins and phase II conjugating enzymes (Ioannides, 2006). In contrast, bovine-specific primer pairs were designed for P450s and phase II enzyme isoform mRNA to be used in the relative quantification by means of quantitative real-time polymerase chain reaction (qPCR).…”

Scientific Opinion on the risk to public health related to the presence of high levels of dioxins and dioxin‐like PCBs in liver from sheep and deer

“…Detailed requirements for methods of sampling and analysis for the official control of levels of dioxins and DL-PCBs in certain foodstuffs are laid down in Commission Regulation (EC) No 1883No /2006 This Regulation contains inter alia a number of provisions concerning methods of sampling depending on the size of the lot, packaging, transport, storage, sealing and labelling.…”

“…CYP1A1 (Olson et al, 1994) and, to a lesser extent, CYP1B1 (Santostefano et al, 1997) are believed to be involved in the oxidative biotransformation of TCDD and related compounds generating -OH derivatives which can be metabolised by UDP glucuronosyltransferase (UGT) to glucuronides that are excreted via the biliary and urinary routes. In rodents and in humans only CYP1A2 is constitutively expressed to a notable extent in the liver, while CYP1A1 and CYP1B1 are predominantly expressed in extra-hepatic tissues (Ioannides, 2006).…”