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^-1 MeHg 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.