Alpha-lipoic acid reduces methylmercury-induced neuronal injury in rat cerebral cortex via antioxidation pathways.
Methylmercury (MeHg), an extremely dangerous environmental pollutant, accumulating preferentially in central nervous system, causes a series of cytotoxic effects. The present study explored the mechanisms which contribute to MeHg-induced neurotoxicity focusing on the oxidative stress in rat cerebral cortex. In addition, the protective effects of alpha-lipoic acid (LA), a potent antioxidant on MeHg-mediated neuronal injury, was also investigated in current study. A MeHg poisoning model was established as 64 rats randomly divided into 4 groups of which saline control group, MeHg-treated groups (4 and 12 μmol kg-1), and LA pretreatment (35 μmol kg-1) group, respectively. After administration of 12 μmol kg-1MeHg for 4 weeks, it was found that obvious pathological changes and apoptosis in neuronal cells. Meanwhile, total Hg levels elevated significantly, superoxide dismutase (SOD) and gluthathione peroxidase (GSH-Px) activities were inhibited, and ROS formation elevated, which might be critical to aggravate oxidative stress in cerebral cortex. In addition, NF-E2-related factor 2 (Nrf2) pathways were activated, as heme oxygenase-1 (HO-1) and γ-glutamylcysteine synthetase heavy subunit (γ-GCSh) expressions were up-regulated obviously by MeHg exposure. Moreover, activities of Na+-K+-ATPase and Ca2+-ATPase were inhibited, leading to intracellular calcium (Ca2+) overload. LA pre-treatment partially reduced MeHg neurotoxic effects via anti-oxidation pathways. In conclusion, these findings clearly indicated that MeHg aggravated oxidative stress and Ca2+overload in cerebral cortex. LA possesses the ability to prevent MeHg neurotoxicity through its anti-oxidative properties. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 931-943, 2017.
Department of Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning Province, 110122, People's Republic of China.
Tianyao
T
Yang
Department of Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning Province, 110122, People's Republic of China.
Zhaofa
Z
Xu
Department of Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning Province, 110122, People's Republic of China.
Wei
W
Liu
Department of Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning Province, 110122, People's Republic of China.
Shu
S
Feng
Department of Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning Province, 110122, People's Republic of China.
Hongpeng
H
Li
Department of Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning Province, 110122, People's Republic of China.
Meixin
M
Guo
Department of Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning Province, 110122, People's Republic of China.
Yu
Y
Deng
Department of Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning Province, 110122, People's Republic of China.
Bin
B
Xu
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008767:Methylmercury Compounds / Q000633:toxicity*; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology*
D000975:Antioxidants; D008767:Methylmercury Compounds; D051267:NF-E2-Related Factor 2; D017382:Reactive Oxygen Species; D008063:Thioctic Acid; D005979:Glutathione Peroxidase; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium
Nrf2 pathway; alpha-lipoic acid; calcium overload; methylmercury; oxidative stress