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

ß-zearalenol (ß-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 ß-zol and HT-2 on bovine ovarian granulosa cells (BGCs), and how melatonin may counteract these effects. ß-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.