The Effect of Selenium on CYP450 Isoform Activity and Expression in Pigs
| Autor: | Zhihui Jiang, Gu Lingbiao, Liang Xiuli, Baorui Cao, Jingmiao Zhang, Xiao Guo |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
medicine.medical_specialty
Swine Endocrinology Diabetes and Metabolism Clinical Biochemistry Administration Oral chemistry.chemical_element 010501 environmental sciences 01 natural sciences Biochemistry Gene Expression Regulation Enzymologic Inorganic Chemistry 03 medical and health sciences Sodium Selenite Cytochrome P-450 Enzyme System Pharmacokinetics Internal medicine medicine Animals RNA-Seq 0105 earth and related environmental sciences chemistry.chemical_classification 0303 health sciences Dose-Response Relationship Drug 030302 biochemistry & molecular biology Biochemistry (medical) CYP1A2 General Medicine Dextromethorphan CYP2E1 Isoenzymes Endocrinology Enzyme chemistry Phenacetin Chlorzoxazone Selenium medicine.drug |
| Zdroj: | Biological Trace Element Research. 196:454-462 |
| ISSN: | 1559-0720 0163-4984 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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