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

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.

Therapeutic effects of astragaloside IV and Astragalus spinosus saponins against bisphenol A-induced neurotoxicity and DNA damage in rats.

BACKGROUND: Bisphenol A (BPA) is an endocrine disruptor to which humans are often subjected during daily life. This study aimed to investigate the ameliorative effect of astragaloside IV (ASIV) or saponins extracted from Astragalus spinosus (A. spinosus) against DNA damage and neurotoxic effects induced by BPA in prefrontal cortex (PFC), hippocampal and striatal brain regions of developing male rats. MATERIALS AND METHODS: Juvenile PND20 (pre-weaning; age of 20 days) male Sprague Dawley rats were randomly and equally divided into four groups: control, BPA, BPA+ASIV and BPA+A. spinosus saponins groups. Bisphenol A (125 mg/kg/day) was administrated orally to male rats from day 20 (BPA group) and along with ASIV (80 mg/kg/day) (BPA+ASIV group) or A. spinosus saponin (100 mg/kg/day) (BPA+ A. spinosus saponins group) from day 50 to adult age day 117. RESULTS: Increased level of nitric oxide (NO) and decreased level of glutamate (Glu), glutamine (Gln), glutaminase (GA) and glutamine synthetase (GS) were observed in the brain regions of BPA treated rats compared with the control. On the other hand, co-administration of ASIV or A. spinosus saponin with BPA considerably improved levels of these neurochemicals. The current study also revealed restoration of the level of brain derived neurotrophic factor (BDNF) and N-methyl-D-aspartate receptors (NR2A and NR2B) gene expression in BPA+ ASIV and BPA+A. spinosus saponins groups. The co-treatment of BPA group with ASIV or A. spinosus saponin significantly reduced the values of comet parameters as well as the intensity of estrogen receptors (ERs) immunoreactive cells and improved the histological alterations induced by BPA in different brain regions. CONCLUSION: It could be concluded that ASIV or A. spinosus saponins has a promising role in modulating the neurotoxicity and DNA damage elicited by BPA.