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

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Abstract

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.

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Acknowledgments

We are grateful to the National Key R&D Program of China (2017YFD0501003), Key Projects of Universities in Henan (19B180001), and Science and Technology of Anyang city (2019).

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Authors and Affiliations

  1. Henan Joint International Research Laboratory of Veterinary Biologics Research and Application, Anyang Institute of Technology, Anyang, 455000, Henan, China

    Zhihui Jiang, Lingbiao Gu, Xiuli Liang, Baorui Cao, Jingmiao Zhang & Xiao Guo

  2. College of Food and Biological Engineering, Anyang Institute of Technology, Huang he Road 22, Anyang, 455000, Henan, China

    Xiao Guo

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  1. Zhihui Jiang
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Correspondence to Xiao Guo.

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The experimental protocol was reviewed and approved by the Ethics Committee of the Institute of Modern Biotechnology for the Uses of Laboratory Animals.

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Jiang, Z., Gu, L., Liang, X. et al. The Effect of Selenium on CYP450 Isoform Activity and Expression in Pigs. Biol Trace Elem Res 196, 454–462 (2020). https://doi.org/10.1007/s12011-019-01945-7

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  • DOI: https://doi.org/10.1007/s12011-019-01945-7

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