Bisphenol A (BPA), an endocrine disruptor, is widely used in the manufacture of different daily life products. Accumulating evidence supports the association between the increasing incidence of neurodegenerative diseases and the BPA level in the environment. In the present study, we aimed to evaluate the neuroprotective role of melatonin against BPA-induced mitochondrial dysfunction–mediated apoptosis in the brain. Herein, adult Sprague Dawley rats were administrated (subcutaneously) with BPA (100 μg/kg BW, 1 mg/kg BW, and 10 mg/kg BW) and melatonin (4 mg/kg BW) for 16 days. Our results showed BPA exposure significantly increased the oxidative stress as demonstrated by increased free radicals (ROS), TBARs level, disrupted cellular architecture, and decreased antioxidant enzymes including SOD, CAT, APX, POD, and GSH levels. Additionally, BPA treatment increased the expression of PUMA, p53, and Drp-1 resulting in apoptosis in the brain tissue of rats. However, melatonin treatment significantly attenuated BPA-induced toxic effects by scavenging ROS, boosting antioxidant enzyme activities, and interestingly enervated brain apoptosis by normalizing p53, PUMA, and Drp-1 expressions at both transcriptional and translational level. Moreover, the brain tissue histology also revealed the therapeutic potential of melatonin by normalizing the cellular architecture. Conclusively, our finding suggests that melatonin could alleviate oxidative stress and mitochondrial dysfunction–linked apoptosis, rendering its neuroprotective potential against BPA-induced toxicity.
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Faculty of Biological Sciences QAU, HEC Pakistan and School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, China
Higher Education Commission Pakistan and Quaid-i-Azam University, URF (University research fund) to Dr. Iram Murtaza
The present study is in compliance with international ethical standards and was carried out according to the guidelines of the National Institute of Health (NIH guidelines Islamabad, Pakistan). The study was conducted according to the guidelines of the Ethical Committee of Quaid-i-Azam University, Islamabad and as per the considerations of U.K. Animals (Scientific Procedures) Act, 1986.
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Ishtiaq, A., Ali, T., Bakhtiar, A. et al. Melatonin abated Bisphenol A–induced neurotoxicity via p53/PUMA/Drp-1 signaling. Environ Sci Pollut Res 28, 17789–17801 (2021). https://doi.org/10.1007/s11356-020-12129-5