Hatipoglu Durmus, Burak Ates Mehmet, Senturk Goktug, Koca Oguzcan, Bulut Aysegul, Donmez Nurcan
Faculty of Veterinary Medicine, Department of Physiology, Selcuk University, Konya, 42130, Türkiye.
Faculty of Veterinary Medicine, Department of Pathology, Selcuk University, 42130, Konya, Türkiye.
Sci Rep. 2025 Jul 2;15(1):22477. doi: 10.1038/s41598-024-80654-1.
The primary objective of this study was to investigate the adverse effects of Bisphenol-A (BPA) on the central and peripheral nervous systems at molecular, histopathological, and immunohistochemical levels, as well as to evaluate the potential neuroprotective effects of Nigella Sativa seed oil (NSO). Rats were administered BPA at a dosage of 100 mg/kg body weight per day via gavage for 30 days, alongside NSO at a dosage of 5 ml/kg body weight per day for the same duration. Rats were sacrificed 24 h after the final administration, and molecular, histopathological, and immunohistochemical examinations were conducted on brain and sciatic nerve tissues. BPA exposure resulted in neurotoxic effects in both the central nervous system (brain) and peripheral nervous system (sciatic nerve), leading to oxidative stress, apoptosis, and neurodegeneration. Specifically, glutathione (GSH) levels decreased, while malondialdehyde (MDA) levels increased in both tissues due to BPA administration. Additionally, BPA elevated the gene expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), Caspase-3, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) mRNA transcripts, while decreasing the expression of nuclear receptor subfamily 4 group A member 2 (NR4A2). In contrast, NSO administration alongside BPA increased GSH content in both tissues and significantly reduced MDA levels. Moreover, NSO decreased the gene expression levels of Nrf2, NF-κB, and Caspase-3 mRNA transcripts, while increasing NR4A2 expression. Furthermore, the neurodegenerative manifestations induced by BPA-such as neuronal degeneration, necrosis, neuronophagy, hemorrhage, gliosis, and elevated glial fibrillary acidic protein (GFAP) levels in the brain-were mitigated by the concurrent administration of NSO, indicating its neuroprotective efficacy. In conclusion, this study provides promising evidence that NSO may therapeutically alleviate BPA-induced neurodegeneration.
本研究的主要目的是在分子、组织病理学和免疫组织化学水平上研究双酚A（BPA）对中枢和外周神经系统的不良影响，以及评估黑种草籽油（NSO）的潜在神经保护作用。大鼠每天经口灌胃给予剂量为100mg/kg体重的BPA，持续30天，同时每天给予剂量为5ml/kg体重的NSO，持续相同时间。在最后一次给药后24小时处死大鼠，并对脑和坐骨神经组织进行分子、组织病理学和免疫组织化学检查。BPA暴露导致中枢神经系统（脑）和外周神经系统（坐骨神经）出现神经毒性作用，导致氧化应激、细胞凋亡和神经退行性变。具体而言，由于给予BPA，两种组织中的谷胱甘肽（GSH）水平降低，而丙二醛（MDA）水平升高。此外，BPA使核因子红细胞2相关因子2（Nrf2）、半胱天冬酶-3（Caspase-3）和活化B细胞的核因子κ轻链增强子（NF-κB）mRNA转录物的基因表达水平升高，同时降低核受体亚家族4 A组成员2（NR4A2）的表达。相比之下，与BPA同时给予NSO可增加两种组织中的GSH含量，并显著降低MDA水平。此外，NSO降低了Nrf2、NF-κB和Caspase-3 mRNA转录物的基因表达水平，同时增加了NR4A2的表达。此外，BPA诱导的神经退行性表现，如脑内神经元变性、坏死、神经元吞噬、出血、胶质细胞增生以及胶质纤维酸性蛋白（GFAP）水平升高，通过同时给予NSO得到缓解，表明其神经保护功效。总之，本研究提供了有前景的证据，表明NSO可能在治疗上减轻BPA诱导的神经退行性变。
