PMID- 30870695 OWN - NLM STAT- MEDLINE DCOM- 20190711 LR - 20190711 IS - 1872-7077 (Electronic) IS - 1382-6689 (Linking) VI - 68 DP - 2019 May TI - Melatonin alleviates beta-zearalenol and HT-2 toxin-induced apoptosis and oxidative stress in bovine ovarian granulosa cells. PG - 52-60 LID - S1382-6689(18)30398-3 [pii] LID - 10.1016/j.etap.2019.03.005 [doi] AB - beta-zearalenol (beta-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 beta-zol and HT-2 on bovine ovarian granulosa cells (BGCs), and how melatonin may counteract these effects. beta-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. CI - Copyright (c) 2019 Elsevier B.V. All rights reserved. FAU - Yang, Fangxiao AU - Yang F AD - College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China. FAU - Li, Lian AU - Li L AD - College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China. FAU - Chen, Kunlin AU - Chen K AD - College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China. FAU - Li, Chengmin AU - Li C AD - College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China. FAU - Wang, Yiru AU - Wang Y AD - College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China. FAU - Wang, Genlin AU - Wang G AD - College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China. Electronic address: glwang@njau.edu.cn. LA - eng PT - Journal Article DEP - 20190307 PL - Netherlands TA - Environ Toxicol Pharmacol JT - Environmental toxicology and pharmacology JID - 9612020 RN - 0 (Antioxidants) RN - 0 (zearalenol) RN - 76LO2L2V39 (Zeranol) RN - I3FL5NM3MO (T-2 Toxin) RN - JL5DK93RCL (Melatonin) RN - NC6C26RM46 (HT-2 toxin) SB - IM MH - Animals MH - Antioxidants/*pharmacology MH - Apoptosis/drug effects MH - Cattle MH - Cells, Cultured MH - Female MH - Granulosa Cells/*drug effects/metabolism MH - Melatonin/*pharmacology MH - Oxidative Stress/drug effects MH - T-2 Toxin/*analogs & derivatives/toxicity MH - Zeranol/*analogs & derivatives/toxicity OTO - NOTNLM OT - Alleviation effect OT - Apoptosis OT - HT-2 toxin OT - Melatonin OT - Oxidative stress OT - beta-zearalenol EDAT- 2019/03/15 06:00 MHDA- 2019/07/12 06:00 CRDT- 2019/03/15 06:00 PHST- 2018/09/20 00:00 [received] PHST- 2019/02/28 00:00 [revised] PHST- 2019/03/05 00:00 [accepted] PHST- 2019/03/15 06:00 [pubmed] PHST- 2019/07/12 06:00 [medline] PHST- 2019/03/15 06:00 [entrez] AID - S1382-6689(18)30398-3 [pii] AID - 10.1016/j.etap.2019.03.005 [doi] PST - ppublish SO - Environ Toxicol Pharmacol. 2019 May;68:52-60. doi: 10.1016/j.etap.2019.03.005. Epub 2019 Mar 7.