Comparative expression of liver cytochrome P450-dependent monooxygenases in the horse and in other agricultural and laboratory species.
Abstract: The apoprotein expression and the catalytic activities of cytochrome P450s involved in the biotransformation of xenobiotics were investigated in horse liver microsomes and compared with those of food producing (cattle, pigs, broiler chicks, and rabbits) and laboratory species (rats). Western blot analysis revealed the presence of proteins immunorelated to rat CYP 1A, CYP 2B, CYP 2E, and CYP 3A subfamilies in hepatic microsomes from horses and from any other examined species. With the exception of the N-demethylation of N-nitrosodimethylamine in broiler chicks, all the recorded interspecies differences were quantitative in nature. Equine preparations proved the most active in the biotransformation of the CYP 1A substrates ethoxy- and methoxyresorufin and the least active in the metabolism of aminopyrine and ethoxycoumarin. On a comparative basis, large differences were observed in the rate of the in vitro metabolism of model substrates between "minor" (rabbits, horses) and "major" food producing species. Taken in due consideration the limitations of the in vitro approach, results from this study reinforce the conclusion that studies on drug efficacy and residue depletion should be performed in each target species.
Publication Date: 2003-03-06 PubMed ID: 12618071DOI: 10.1016/s1090-0233(02)00174-0Google Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research compares the performance of cytochrome P450s, proteins involved in processing unknown substances, in horse liver with that of other animals’ livers, including both farm and laboratory animals. It concludes the differences identified could impact how each species responds to drugs, reinforcing the need to trial any veterinary treatments in the specific species it is intended for.
Overview of the Study
- The research investigates and compares the expression and action of cytochrome P450 (CYP), a group of enzymes critical in metabolising substances in the body, specifically in the liver. The focus is on horses and a comparison is made with food-producing (cattle, pigs, poultry, rabbits) and lab animals (rats).
Methodology and Results
- The researchers used a technique called ‘Western blot analysis’ to identify proteins in liver microsomes (tiny liver fragments used to study metabolism of drugs) that were related to a certain rat CYP subfamilies.
- The proteins were found in all the animals studied, but the degree to which they were expressed and their level of activity differed among species. The horse liver microsomes were most active when metabolizing specific substrates but were less active with others.
Significance and Conclusions
- The findings show varying rates of metabolism for different substrates between what are described as ‘minor’ (rabbits, horses) and ‘major’ (larger food production species). This indicates that the reactions of the liver – and thus potentially the whole organism – to drugs can differ markedly between species.
- Notably, the study found that the in vitro (laboratory-based, outside of the living organism) actions of these enzymes do not always reflect the in vivo (within the living organism) actions. This suggests that in vitro experiments should not be the sole basis for drug-testing and similar.
- In conclusion, the researchers suggest that these findings reinforce the idea that drug efficacy and the diminishment of drug residues should be studied in each individual target species to ensure safety and effectiveness.
Cite This Article
APA
Nebbia C, Dacasto M, Rossetto Giaccherino A, Giuliano Albo A, Carletti M.
(2003).
Comparative expression of liver cytochrome P450-dependent monooxygenases in the horse and in other agricultural and laboratory species.
Vet J, 165(1), 53-64.
https://doi.org/10.1016/s1090-0233(02)00174-0 Publication
Researcher Affiliations
- Department of Animal Pathology, Division of Pharmacology and Toxicology, University of Turin, Grugliasco, Italy. cnebbia@veter.unito.it
MeSH Terms
- Animals
- Animals, Domestic / metabolism
- Animals, Laboratory / metabolism
- Blotting, Western
- Cattle
- Chickens / metabolism
- Cytochrome P-450 Enzyme System / metabolism
- Horses / metabolism
- Liver / enzymology
- Rabbits
- Rats
- Species Specificity
- Swine / metabolism
Citations
This article has been cited 17 times.- Ichinose P, Miró MV, Larsen K, Lanusse C, Lifschitz A, Virkel G. Medication with fenbendazole in feed: plasma concentrations and effects on hepatic xenobiotic metabolizing enzymes in swine. Vet Res Commun 2023 Jun;47(2):803-815.
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- Ichinose P, Munafó JP, Miró MV, Valente M, Moreno-Torrejón L, Larsen K, Lanusse C, Lifschitz A, Virkel G. Effects of Newer Veterinary Macrolide Antimicrobials on the CYP3A-Dependent Metabolism in Cattle Liver Microsomes: Potential Metabolic Drug-Drug Interaction with Monensin. Animals (Basel) 2026 Jan 25;16(3).
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