Alpha-lipoic acid protects against methylmercury-induced neurotoxic effects via inhibition of oxidative stress in rat cerebral cortex

• We observed the effects of methylmercury on excitotoxicity and oxidative damage.
• Alpha-lipoic acid antagonized the oxidative damage of methylmercury obviously.
• We explored the relationship between excitotoxicity and oxidative damage.
• We explored the mechanisms of alpha-lipoic acid protective effects.

MeHg is one of the environmental pollutants that lead to oxidative stress and an indirect excitotoxicity caused by altered glutamate (Glu) concentration. However, little was known of the interaction. Therefore, we developed a rat model of MeHg poisoning to explore its neurotoxic effects, and whether LA could attenuate MeHg-induced neurotoxicity. Seventy-two rats were randomly divided into four groups: control group, MeHg-treated groups (4 and 12 μmol/kg), and LA pre-treatment group. Administration of the 12 μmol/kg MeHg for 4 weeks significantly increased ROS formation that might be critical to aggravate oxidative damages in cerebral cortex. Meanwhile, Glu metabolism as well as GLAST and GLT-1 appeared to be disrupted by MeHg exposure. Pre-treatment of the 35 μmol/kg LA significantly prevented MeHg-induced oxidative stress and Glu dyshomoestasis.In conclusion, findings indicated that MeHg could induce oxidative stress and Glu uptake/metabolism disorders in cerebral cortex, LA might antagonize these neurotoxic effects induced by MeHg.