Neurotoxicity and neuroinflammatory effects of bisphenol A in male rats: the neuroprotective role of grape seed proanthocyanidins

Abstract

Exposure to bisphenol A (BPA) contributes to neurological disorders, but the underlying mechanisms are still not completely understood. We studied the neurotoxic effect of BPA and how it promotes inflammation and alteration in the neurotransmission synthesis, release, and transmission. This study was also designed to investigate the neuroprotective effect of grape seed proanthocyanidins (GSPE) against BPA-induced neurotoxicity in rats. Rats were equally divided into 4 groups with 7 rats in each: control group, BPA group, GSPE + BPA group, and GSPE group. Rats were orally treated with their respective doses (50 mg BPA/kg BW and/or 200 mg GSPE/kg BW) daily for 70 days. BPA elicits significant elevation in malondialdehyde (MDA) and nitric oxide (NO) associated with a significant reduction in glutathione (GSH), total thiols, glutathione peroxidase (GPx), superoxide dismutase (SOD), and glutathione-S-transferase (GST). BPA exposure results in increased dopamine and serotonin levels, elevation in acetylcholinesterase (AChE) activity, and reduction in Na/K-ATPase and total ATPase activities in the brain. Also, BPA induces upregulation in the gene expression of the inflammatory markers, tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2), and in the tumor suppressor and pro-oxidant p53 protein. The pretreatment with GSPE attenuates or ameliorate all the oxidative and neurotoxic parameters induced by BPA. Our results suggest that GSPE has a promising role in modulating BPA-induced neuroinflammation and neurotoxicity and its antioxidant and free radical scavenging activities may in part be responsible for such effects.

Keywords: Bisphenol A; COX-2; Grape seed proanthocyanidins; Na/K-ATPase; Oxidative stress; TNF-α.