Protective effect of proanthocyanidin on mice Sertoli cell apoptosis induced by zearalenone via the Nrf2/ARE signalling pathway

Environ Sci Pollut Res Int. 2017 Dec;24(34):26724-26733. doi: 10.1007/s11356-017-0123-y. Epub 2017 Sep 27.

Abstract

This study evaluated the protective effect of proanthocyanidin (PC) on the cytotoxicity of the Sertoli cell TM4 of mice, as induced by zearalenone (ZEA). Flow cytometry was used to detect the apoptosis rate of cells in each group. The activities of antioxidant enzymes and the content of antioxidant substances were detected by using a proprietary kit; the RT-PCR method was used to detect the expression level of mRNA, the related genes of Nrf2/ARE signal pathway, the nuclear factor E2 related factor 2 (Nrf2), heme oxygenase 1 (HO-1), glutathione peroxidase (GSH-Px), quinone oxidoreductase 1 (NQO1), γ-glutamylcysteine synthetase (γ-GCS) and the expression level of mRNA, the apoptosis-related genes, Bcl-2 and Bax; the Western-blot method was used to detect the protein expression levels of Nrf2, GSH-Px, HO-1, γ-GCS and NQO1 in each group. Our results showed that PC could reduce the apoptosis rate of the TM4 cells exposed to ZEA (p < 0.01); PC could enhance the decrease in the activities of T-SOD and GSH-Px induced by ZEA (p < 0.05), reduce the increase in the content of MDA, as caused by ZEA; PC could significantly up-regulate the down-regulation levels of the mRNA and protein of Nrf2, GSH-Px, HO-1, γ-GCS and NQO1 induced by ZEA. PC could enhance the decrease in the mRNA expression level of Bcl-2 and down-regulate the mRNA expression of Bax induced by ZEA (p < 0.05). These results demonstrated that PC conferred protective effects against oxidative damage and apoptosis of TM4 cells induced by ZEA. The protection mechanism of PC on TM4 cells might act through the activation of the Nrf2/ARE signalling pathway.

Keywords: Cell apoptosis; Nrf2/ARE signalling pathway; Oxidative damage; Proanthocyanidins; TM4 cell; Zearalenone.

MeSH terms

  • Animals
  • Antioxidant Response Elements / drug effects*
  • Antioxidants / metabolism
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line
  • Cell Survival / drug effects
  • Male
  • Mice
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress / drug effects
  • Proanthocyanidins / pharmacology*
  • Sertoli Cells / drug effects*
  • Sertoli Cells / pathology
  • Signal Transduction / drug effects
  • Up-Regulation
  • Zearalenone / toxicity

Substances

  • Antioxidants
  • NF-E2-Related Factor 2
  • Proanthocyanidins
  • proanthocyanidin
  • Zearalenone