Melatonin alleviates β-zearalenol and HT-2 toxin-induced apoptosis and oxidative stress in bovine ovarian granulosa cells

Environ Toxicol Pharmacol. 2019 May:68:52-60. doi: 10.1016/j.etap.2019.03.005. Epub 2019 Mar 7.

Abstract

β-zearalenol (β-zol) and HT-2 are mycotoxins which cause apoptosis and oxidative stress in mammalian reproductive cells. Melatonin is an endogenous antioxidant involved in apoptosis and oxidative stress-related activities. This study investigated the effects of β-zol and HT-2 on bovine ovarian granulosa cells (BGCs), and how melatonin may counteract these effects. β-zol and HT-2 inhibited cell proliferation in a dose-dependent manner, and induced apoptosis of BGCs. They also yielded upregulation of the apoptosis-related genes Bax/Bcl-2 and Caspase3 and phosphorylation of p38MAPK. Increases in intracellular ROS were observed along with higher levels of mRNA anti-oxidation markers SOD1, SOD2, and CAT. SOD1, SOD2, malonaldehyde (MDA), and glutathione peroxidase (GSH-px) activities increased, as did the levels of SOD1 and SOD2 proteins. All of these effects were reduced or entirely attenuated in BGCs pre-treated with melatonin. Our results demonstrate that melatonin has protective effects against mycotoxin-induced apoptosis and oxidative stress in BGCs.

Keywords: Alleviation effect; Apoptosis; HT-2 toxin; Melatonin; Oxidative stress; β-zearalenol.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects
  • Cattle
  • Cells, Cultured
  • Female
  • Granulosa Cells / drug effects*
  • Granulosa Cells / metabolism
  • Melatonin / pharmacology*
  • Oxidative Stress / drug effects
  • T-2 Toxin / analogs & derivatives*
  • T-2 Toxin / toxicity
  • Zeranol / analogs & derivatives*
  • Zeranol / toxicity

Substances

  • Antioxidants
  • zearalenol
  • Zeranol
  • T-2 Toxin
  • Melatonin
  • HT-2 toxin