The Effect of Selenium on CYP450 Isoform Activity and Expression in Pigs

Selenium is an essential nutrient in diets; however, the effects of selenium on enzyme metabolic activation are not currently clear. Cytochromes P450 (CYP450) are major phase I metabolic enzymes involved in the biotransformation of xenobiotics and endogenous compounds to form electrophilic reactive...

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Bibliographic Details
Published in:Biological trace element research 2020-08, Vol.196 (2), p.454-462
Main Authors: Jiang, Zhihui, Gu, Lingbiao, Liang, Xiuli, Cao, Baorui, Zhang, Jingmiao, Guo, Xiao
Format: Article
Language:English
Subjects:
Acetanilide
Administration, Oral
Animals
Biochemistry
Biomedical and Life Sciences
Biotechnology
Biotransformation
Chlorzoxazone
CYP1A2 protein
Cytochrome P-450 Enzyme System - genetics
Cytochrome P-450 Enzyme System - metabolism
Cytochrome P450
Cytochromes
Cytochromes P450
Dextromethorphan
Dose-Response Relationship, Drug
Drug interaction
Drug interactions
Food-drug interactions
Gene expression
Gene Expression Regulation, Enzymologic - drug effects
Gene Expression Regulation, Enzymologic - genetics
High-performance liquid chromatography
HPLC
Isoenzymes - genetics
Isoenzymes - metabolism
Life Sciences
Liquid chromatography
Metabolic activation
Metabolic rate
Metabolism
Metabolites
Nucleic acids
Nutrition
Oncology
Pharmacokinetics
Phenacetin
Ribonucleic acid
RNA
RNA-Seq
Selenium
Sodium Selenite - administration & dosage
Sodium Selenite - pharmacology
Swine - genetics
Testosterone
Xenobiotics
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Summary:Selenium is an essential nutrient in diets; however, the effects of selenium on enzyme metabolic activation are not currently clear. Cytochromes P450 (CYP450) are major phase I metabolic enzymes involved in the biotransformation of xenobiotics and endogenous compounds to form electrophilic reactive metabolites. To investigate the effect of selenium on CYP450 isoform activity, the Landrace pigs were divided into three groups: the control group (containing Se 0.15 mg/kg), the Se-deficient group (Se 0.03 mg/kg), and the Se-supply group (Se 0.35 mg/kg). After 1 week of administration, a mixed solution (20 mg/kg of dextromethorphan, phenacetin, chlorzoxazone, and 10 mg/kg of testosterone in a CMC-Na solution) was intravenously injected into all pigs. The mixed solution content and pharmacokinetic parameters were assayed by HPLC and DAS, respectively. To investigate the effect of selenium on CYP450 isoform expression, RNA-Seq analysis, Western boltting, and qPCR were used. Results showed that Se-supply group significantly increased the activity and expression of CYP1A2 and CYP2D25, and decreased CYP3A29. Se-deficient group decreased the activity of CYP1A2, CYP2D25, and CYP2E1. These results demonstrated that selenium content affecting the activity or expression of the CYP450 isoform may lead to a food-drug interaction.
ISSN:0163-4984
1559-0720
DOI:10.1007/s12011-019-01945-7