Zinc inhibits the reproductive toxicity of Zearalenone in immortalized murine ovarian granular KK-1 cells

Sci Rep. 2015 Sep 23:5:14277. doi: 10.1038/srep14277.

Abstract

Zearalenone (ZEA) mainly injures the reproductive system of mammals. In the present study, we aimed to explore the mechanism by which zinc inhibits ZEA-induced reproductive damage in KK-1 cells for the first time. The results shown that both zinc sulfate and zinc gluconate addition increased the intracellular zinc concentration and influenced the expression of zinc transporters (Slc30a1 and Slc39a1) in a time-dependent manner. Co-incubation of zinc with ZEA significantly reduced the ZEA-induced reactive oxygen species and malondialdehyde elevation by promoting the transcription of Mtf1 and Mt2. Meanwhile, two different zincs inhibited the ZEA-induced loss of mitochondrial membrane potential and elevation of late-stage apoptosis via activating the mitochondrial apoptotic pathway by recovering the mRNA and protein expression of pro-apoptotic genes (Bax, Casp3, Casp9). Zinc also recovered cells from S-phase cell cycle arrest. In addition, both of them promoted the ZEA-induced estrogen production but regulated the expression of steroidogenic enzymes (Star, Cyp11a1, Hsd3b1, Cyp17a1) in different way. All these results indicated that zinc could inhibit the reproductive toxicity of ZEA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Caspase 3 / biosynthesis
  • Caspase 9 / biosynthesis
  • Cell Line
  • Cell Survival / drug effects*
  • DNA-Binding Proteins / biosynthesis
  • Estrogens / biosynthesis
  • Gluconates / pharmacology
  • Malondialdehyde / metabolism
  • Membrane Potential, Mitochondrial / drug effects*
  • Metallothionein / biosynthesis
  • Mice
  • Mitochondria / metabolism
  • Oxidative Stress / drug effects
  • Reactive Oxygen Species / metabolism
  • S Phase Cell Cycle Checkpoints / drug effects*
  • Transcription Factor MTF-1
  • Transcription Factors / biosynthesis
  • Zearalenone / toxicity*
  • Zinc / pharmacology*
  • Zinc Sulfate / pharmacology
  • bcl-2-Associated X Protein / biosynthesis

Substances

  • Bax protein, mouse
  • DNA-Binding Proteins
  • Estrogens
  • Gluconates
  • Mt2 protein, mouse
  • Reactive Oxygen Species
  • Transcription Factors
  • bcl-2-Associated X Protein
  • Malondialdehyde
  • Zearalenone
  • Zinc Sulfate
  • Metallothionein
  • Casp3 protein, mouse
  • Casp9 protein, mouse
  • Caspase 3
  • Caspase 9
  • Zinc
  • gluconic acid