title: The protective role of tea polyphenols against methylmercury-induced neurotoxic effects in rat cerebral cortex via inhibition of oxidative stress.
abstract: Methylmercury (MeHg) is a ubiquitous environmental contaminant that could induce oxidative stress and an indirect glutamate (Glu)-mediated excitotoxicity. However, the underlying mechanisms through which MeHg affects the central nervous system have not been fully elucidated, and little has been known of the interaction between oxidative stress and Glu dyshomeostasis in MeHg neurotoxicity. Therefore, rats were administrated with different MeHg concentrations (0, 4, and 12 μmol/kg) to evaluate the neurotoxic effects in cerebral cortex. Moreover, we have investigated the neuroprotective role of tea polyphenols (TP), a natural antioxidant that has a formidable free radical scavenge ability, against MeHg-induced neurotoxicity. Eighty rats were randomly divided into five groups: control, TP control, MeHg-treated (4 and 12 μmol/kg), and TP pretreated (1 mmol/kg). Administration of MeHg at 12 μmol/kg for 4 weeks significantly increased total Hg and ROS levels in cerebral cortex. In addition, MeHg reduced non-enzymatic (non-protein sulfhydryl) and enzymatic (SOD and GSH-Px) antioxidants, up-regulated Nrf2, HO-1, and γ-GCS expression. Moreover, MeHg-induced ROS over-production appeared to inhibit the activities of GS, down-regulated GLAST and GLT-1 expression in cerebral cortex. Pretreatment with TP at a dose of 1 mmol/kg significantly prevented MeHg-induced oxidative stress and Glu uptake/metabolism disorders in cerebral cortex. In conclusion, the results suggested that oxidative stress resulting from excessive ROS formation plays a critical role in MeHg neurotoxicity. TP possesses the ability to attenuate MeHg-induced neurotoxic effects through its antioxidative properties.
authors.affiliation: Department of Environmental Health, School of Public Health, China Medical University , Shenyang, Liaoning Province , P. R. China.
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.forename: Z
authors.initials: Z
authors.lastname: Xu
authors.forename: T
authors.initials: T
authors.lastname: Yang
authors.forename: Y
authors.initials: Y
authors.lastname: Deng
authors.forename: B
authors.initials: B
authors.lastname: Xu
authors.forename: S
authors.initials: S
authors.lastname: Feng
authors.forename: Y
authors.initials: Y
authors.lastname: Li
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D008297:Male; D008767:Methylmercury Compounds / Q000633:toxicity*; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects*; D059808:Polyphenols / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013662:Tea / Q000737:chemistry
chemical_list: D000199:Actins; D005609:Free Radicals; D008767:Methylmercury Compounds; D059808:Polyphenols; D017382:Reactive Oxygen Species; D013662:Tea
keywords: glutamate uptake/metabolism; methylmercury; oxidative stress; reactive oxygen species; tea polyphenols