Selenium alleviates porcine nephrotoxicity of ochratoxin A by improving selenoenzyme expression in vitro

PLoS One. 2015 Mar 24;10(3):e0119808. doi: 10.1371/journal.pone.0119808. eCollection 2015.

Abstract

Ochratoxin A (OTA), a mycotoxin, is a potent nephrotoxin in humans and animals. Selenium (Se) is an essential micronutrient for humans and animals, and plays a key role in antioxidant defense. To date, little is known about the effect of Se on OTA-induced nephrotoxicity. In this study, the protective effects of selenomethionine against OTA-induced nephrotoxicity were investigated using the porcine kidney 15 (PK15) cells as a model. The results showed that OTA induced nephrotoxicity in a dose-dependent manner. Se at 0.5, 1, 2 and 4 μM had significant protective effects against OTA-induced nephrotoxicity. Furthermore, selenomethionine enhanced the activity and mRNA and protein expression of glutathione peroxidase 1 (GPx1), mRNA expression of GPx4, and mRNA expression of thioredoxin reductase 1 in the presence and absence of OTA. Among them, promoting effect of selenomethionine on GPx1 was maximal. Knock-down of GPx1 by using a GPx1-specific siRNA eliminated the protective effects of selenomethionine against OTA-induced nephrotoxicity. The results suggest that selenomethionine alleviates OTA-induced nephrotoxicity by improving selenoenzyme expression in PK15 cells. Therefore, selenomethionine supplementation may be an attractive strategy for protecting humans and animals from the risk of kidney damage induced by OTA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Apoptosis / drug effects
  • Cell Line
  • Dietary Supplements / analysis
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Gene Knockdown Techniques
  • Kidney / cytology
  • Kidney / drug effects*
  • Ochratoxins / toxicity*
  • Oxidative Stress / drug effects
  • Oxidoreductases / deficiency
  • Oxidoreductases / genetics*
  • RNA, Small Interfering / genetics
  • Selenomethionine / pharmacology*
  • Swine

Substances

  • Antioxidants
  • Ochratoxins
  • RNA, Small Interfering
  • ochratoxin A
  • Selenomethionine
  • Oxidoreductases

Grants and funding

This work was funded by the Natural Science Foundation of China (Grant number, 31272627), the Natural Science Foundation of Jiangsu Province (Grant number, BK 2012772), and the Priority Academic Program Development of Jiangsu Higher Education Institutions. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.