Cytochrome P450 1A-dependent activities in deer, cattle and horses.
Abstract: The objective of this study was to investigate and characterize the metabolic activities of CYP1A in deer, cattle and horses in comparison to those of rats using ethoxyresorufin O-deethylation (EROD) and methoxyresorufin O-demethylation (MROD) assays. We performed an inhibition study for these activities using anti-rat CYP1A1 antibody and identified that these activities were due to the CYP1A subfamily. Interspecies differences in the CYP1A-dependent activities were highly observed in this study. In particular, we found that the horse had the highest EROD and MROD activities among the examined animal species. In the kinetic analysis, the horses showed the highest Vmax and catalytic efficiency (Vmax/Km), followed by the cattle, deer and rats.
Publication Date: 2010-01-13 PubMed ID: 20068271DOI: 10.1292/jvms.09-0318Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The researchers explored and mapped out the metabolic activities of a type of Cytochrome P450 (CYP1A) in deer, cattle, horses and rats. The study showed different CYP1A-dependent activities across the species, with horses exhibiting significantly higher metabolic activities compared to the other animals.
Investigation and Characterization of CYP1A Metabolic Activities Across Species
- The primary goal of the research was to study and provide detailed insight into the metabolic activities of CYP1A in four different animals: deer, cattle, horses, and rats. Cytochrome P450 (specifically CYP1A) is a crucial enzyme involved in drug metabolism and is largely expressed in the liver tissue of animals.
- The researchers used Ethoxyresorufin O-deethylation (EROD) and Methoxyresorufin O-demethylation (MROD) tests as methods to examine these metabolic activities. These tests are well-known methods used for measurement of CYP enzyme activity.
Identification of CYP1A-Dependent Activities
- An inhibition study was carried out using an anti-rat CYP1A1 antibody to ascertain if the observed metabolic activities came directly from the CYP1A subfamily.
- The results confirmed that the activities detected were due to the CYP1A subfamily, a group of closely-related P450s that contribute to the metabolism of certain substances in these animals.
Interspecies Differences in CYP1A-Dependent Activities
- The research showed marked differences in the CYP1A-dependent activities between the four animal species being studied. This indicated diverse metabolic capacities among these animals that could lead to different pharmacokinetic responses to drugs.
- Horses demonstrated the highest level of both EROD and MROD activities of the species studied, indicating a significantly higher metabolic rate.
Kinetic Analysis of Metabolic Activities Across Species
- The research included a kinetic analysis to determine the rate of metabolic reactions. This study noted that horses showed the highest maximum rate of an enzyme-catalysed reaction (Vmax) and the highest catalytic efficiency (Vmax/Km).
- The order of species from highest to lowest metabolic activities and efficiencies were horses, cattle, deer, and then rats. This finding could impact how drugs and therapies are designed for these species, as the metabolic rate could affect drug effectiveness and toxicity.
Cite This Article
APA
Darwish WS, Ikenaka Y, Eldaly EA, Ohno M, Sakamoto KQ, Fujita S, Ishizuka M.
(2010).
Cytochrome P450 1A-dependent activities in deer, cattle and horses.
J Vet Med Sci, 72(5), 561-566.
https://doi.org/10.1292/jvms.09-0318 Publication
Researcher Affiliations
- Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita-ku, Sapporo, Japan. ishizum@vetmed.hokudai.ac.jp
MeSH Terms
- Animals
- Cattle
- Cytochrome P-450 CYP1A1 / antagonists & inhibitors
- Cytochrome P-450 CYP1A1 / metabolism
- Cytochrome P-450 CYP1A2 / metabolism
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Enzyme System / metabolism
- Deer
- Horses
- Kinetics
- Microsomes, Liver / enzymology
- Rats
- Species Specificity
Citations
This article has been cited 5 times.- Shinya S, Yohannes YB, Ikenaka Y, Nakayama SM, Ishizuka M, Fujita S. Characteristics of cytochrome P450-dependent metabolism in the liver of the wild raccoon, Procyon lotor. J Vet Med Sci 2022 Dec 14;84(12):1665-1672.
- Darwish WS, Chiba H, Elhelaly AE, Hui SP. Estimation of cadmium content in Egyptian foodstuffs: health risk assessment, biological responses of human HepG2 cells to food-relevant concentrations of cadmium, and protection trials using rosmarinic and ascorbic acids. Environ Sci Pollut Res Int 2019 May;26(15):15443-15457.
- Gleich A, Kaiser B, Honscha W, Fuhrmann H, Schoeniger A. Evaluation of the hepatocyte-derived cell line BFH12 as an in vitro model for bovine biotransformation. Cytotechnology 2019 Feb;71(1):231-244.
- Nagasue R, Murata I, Sasaki K, Sakai R, Miyajima H, Shimoda M. Effectiveness of the liver micronucleus assay using juvenile mice. J Vet Med Sci 2017 Jul 28;79(7):1310-1317.
- Dhamankar V, Assem M, Donovan MD. Gene expression and immunochemical localization of major cytochrome P450 drug-metabolizing enzymes in bovine nasal olfactory and respiratory mucosa. Inhal Toxicol 2015;27(14):767-77.
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