Department of Medical Elementology and Toxicology, Jamia Hamdard, New Delhi, 110062, India.
Molecular Sciences Laboratory, National Institute of Immunology, New Delhi, 110067, India.
Neurochem Int. 2018 Sep;118:166-175. doi: 10.1016/j.neuint.2018.06.005. Epub 2018 Jun 13.
Bisphenol A (BPA), a well-known xenoestrogen, is ubiquitously utilized in manufacturing of polycarbonated plastics. Convincing evidence suggests that BPA induces neurotoxicity and certain behavioral deficits. α-Lipoic acid (ALA) supplementation has shown protective effect against heart and liver diseases, diabetes, and neurological debility associated with aging. We studied the neuromodulatory effect of ALA against neurotoxicity of BPA in vitro in C8-D1A mouse astrocyte cell line and in vivo in C57BL/6J male mice. In vitro ALA (100 μM) protected cells from BPA (30 μM)-induced reactive oxygen species generation and increased activity of glial fibrillary acidic protein. ALA showed reduction in cell death in astrocytes treated with BPA. In vivo ALA (50 mg/kg) increased the neurospecific acetylcholinesterase activity and decreased the monoamine oxidase activity altered by BPA exposure (10 mg/kg, per os x 30 days). In addition to neuroprotective effects, ALA also showed protective effects against BPA-induced oxidative stress. We observed that ALA significantly replenished the declined neurobehavioral and cognitive performances, decreased muscle coordination and alerted short-term recognition memory in mice exposed to BPA. Our results suggest that ALA has a promising role in modulating BPA-induced neurotoxicity in C8-D1A mouse astrocyte cells as well as neurochemical and neurobehavioral deficits in C57BL/6J male mice and its antioxidant and free radical scavenging activities may in part be responsible for such an effect.
双酚 A（BPA）是一种众所周知的外源性雌激素，广泛应用于聚碳酸酯塑料的制造。有充分证据表明，BPA 可诱导神经毒性和某些行为缺陷。α-硫辛酸（ALA）补充剂已显示出对与衰老相关的心脏病、肝病、糖尿病和神经虚弱的保护作用。我们研究了 ALA 对体外 C8-D1A 小鼠星形胶质细胞瘤系和体内 C57BL/6J 雄性小鼠中 BPA 神经毒性的神经调节作用。体外 ALA（100µM）可保护细胞免受 BPA（30µM）诱导的活性氧生成，并增加神经胶质纤维酸性蛋白的活性。ALA 显示出对 BPA 处理的星形胶质细胞中细胞死亡的减少。体内 ALA（50mg/kg）增加了神经特异性乙酰胆碱酯酶的活性，并降低了 BPA 暴露（10mg/kg，口服 x 30 天）改变的单胺氧化酶活性。除了神经保护作用外，ALA 还显示出对 BPA 诱导的氧化应激的保护作用。我们观察到，ALA 显著补充了因 BPA 暴露而下降的神经行为和认知表现，降低了肌肉协调性，并提醒了小鼠的短期识别记忆。我们的结果表明，ALA 在调节 C8-D1A 小鼠星形胶质细胞中的 BPA 诱导的神经毒性以及 C57BL/6J 雄性小鼠的神经化学和神经行为缺陷方面具有广阔的前景，其抗氧化和自由基清除活性可能部分负责这种作用。
