Abstract
Abstract Background Fluoride (Fl) exposure engenders neurodegeneration and induces oxidative stress in the brain. Therefore, the mechanism of Fl-induced neurotoxic effects needs to be determined. The aim of this study was to investigate the neuroprotective effects of EGCG (40 mg/kg) on Fl (25 mg/kg/bw)-induced oxidative stress mediated neurotoxicity with special emphasis on the hippocampus (4 weeks). Results Fl-intoxicated rat shows an increased Fl concentration along with the decreased neurotransmitter (AChE, NP, DA and 5-HT) activity in the brain. The oxidative stress markers (ROS, TBARS, NO, and PC) was significantly increased with decreased enzymatic (SOD, CAT, GPx, GR, GST, and G6PD) and nonenzymatic antioxidants (GSH, TSH, and Vit.C) in the rat hippocampus. Moreover, results showed that increases in intrinsic and extrinsic apoptotic pathway leading to DNA damage and cell death were also proved by the immunohistochemical, histological, and ultra-structural studies in the Fl-treated rat hippocampus. In this context, pre-administration of EGCG significantly improved the oxidative stress, biochemical changes, cellular apoptotic and histological alternations by Fl in the hippocampus of rats. Conclusions These results confirmed the EGCG supplementation might attenuate the Fl-induced neurotoxicity via Nrf2/Keap1 signaling pathway in the rat hippocampus.