Abstract
BackgroundBisphenol 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 MethodsJuvenile 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.ResultsIncreased 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.ConclusionIt could be concluded that ASIV or A. spinosus saponins has a promising role in modulating the neurotoxicity and DNA damage elicited by BPA.
Highlights
The intervention in the early developmental stages of the central nervous system (CNS) produces permanent alterations in the brain physiology in different life stages of the exposed animals and their progeny (Manikkam et al, 2013)
A significant (P ≤ 0.05) increase in nitric oxide (NO) concentration and significant decrease in the activities of GA and glutamine synthetase (GS) was observed in the prefrontal cortex (PFC), hippocampus, and striatum of BPAtreated group compared with control
Co-administration of astragaloside IV (ASIV) or A. spinosus saponin with Bisphenol A (BPA) significantly (P ≤ 0.05) reduced the concentration of NO in the mentioned brain regions of these two groups compared with BPA-treated group
Summary
The intervention in the early developmental stages of the central nervous system (CNS) produces permanent alterations in the brain physiology in different life stages of the exposed animals and their progeny (Manikkam et al, 2013). Several studies linked the neurotoxic effects of BPA to its potency to perturb the signaling of estrogen receptor (ER) in developing neurons. 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. 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. It could be concluded that ASIV or A. spinosus saponins has a promising role in modulating the neurotoxicity and DNA damage elicited by BPA
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