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.

Keywords::

• methylmercury
• oxidative stress
• reactive oxygen species
• glutamate uptake/metabolism
• tea polyphenols

Acknowledgments

In addition, we are grateful to Jingyi Sun (The first affiliated hospital of China Medical University) for his technical support.

Declaration of interest

The authors report no declarations interest. The authors alone are responsible for the content and writing of the paper.

This study was supported by the grants from the National Natural Science Foundation of China (No. 81172631).