Selenomethionine Alleviates AFB1-Induced Damage in Primary Chicken Hepatocytes by Inhibiting CYP450 1A5 Expression via Upregulated SelW Expression

J Agric Food Chem. 2017 Mar 29;65(12):2495-2502. doi: 10.1021/acs.jafc.6b05308. Epub 2017 Mar 21.

Abstract

This study aims to evaluate the protective effects of selenomethionine (SeMet) on aflatoxin B1 (AFB1)-induced hepatotoxicity in primary chicken hepatocytes. Cell viability and lactic dehydrogenase activity assays revealed the dose dependence of AFB1 toxicity to chicken hepatocytes. AFB1 concentrations of >0.05 μg/mL significantly reduced glutathione and total superoxide dismutase levels and increased the malondialdehyde concentration and cytochrome P450 enzyme 1A5 (CYP450 1A5) mRNA levels (P < 0.05). AFB1, however, did not affect CYP450 3A37 mRNA levels. Supplementation with 2 μM SeMet protected against AFB1-induced changes and significantly increased selenoprotein W (SelW) mRNA levels (P < 0.05). Additionally, SelW knockdown attenuated the protective effect of SeMet on AFB1-induced damage and significantly increased the level of CYP450 1A5 expression (P < 0.05). Therefore, SeMet alleviates AFB1-induced damage in primary chicken hepatocytes by improving SelW expression, thus inhibiting CYP450 1A5 expression.

Keywords: AFB1; cytochrome P450 enzymes; primary chicken hepatocytes; selenomethionine; selenoprotein W; siRNA.

MeSH terms

  • Aflatoxin B1 / toxicity*
  • Animals
  • Avian Proteins / genetics*
  • Avian Proteins / metabolism
  • Chickens
  • Cytochrome P-450 Enzyme Inhibitors / pharmacology*
  • Cytochrome P-450 Enzyme System / genetics*
  • Cytochrome P-450 Enzyme System / metabolism
  • Glutathione / metabolism
  • Hepatocytes / drug effects*
  • Hepatocytes / enzymology
  • Hepatocytes / metabolism
  • Oxidative Stress / drug effects
  • Selenomethionine / pharmacology*
  • Selenoprotein W / genetics*
  • Selenoprotein W / metabolism
  • Superoxide Dismutase / metabolism
  • Up-Regulation / drug effects

Substances

  • Avian Proteins
  • Cytochrome P-450 Enzyme Inhibitors
  • Selenoprotein W
  • Cytochrome P-450 Enzyme System
  • Selenomethionine
  • Aflatoxin B1
  • Superoxide Dismutase
  • Glutathione