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Melatonin abated Bisphenol A–induced neurotoxicity via p53/PUMA/Drp-1 signaling

Environmental Science and Pollution Research volume 28, pages 17789–17801 (2021)Cite this article

Abstract

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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Data availability

The data and materials of the present study are submitted in main manuscript and in supplementary files; however, if the Journal requires any other relevant data, we will definitely make it available.

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Acknowledgments

Faculty of Biological Sciences QAU, HEC Pakistan and School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, China

Funding

Higher Education Commission Pakistan and Quaid-i-Azam University, URF (University research fund) to Dr. Iram Murtaza

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Authors and Affiliations

  1. Signal Transduction Laboratory, Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan

    Ayesha Ishtiaq, Tahir Ali, Attia Bakhtiar, Robina Bibi, Kinza Bibi, Iram Mushtaq & Iram Murtaza

  2. State Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, China

    Tahir Ali & Shupeng Li

  3. Department of Biotechnology, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, Pakistan

    Wajiha Khan

  4. Faculty of Biological Sciences, Hazara University, Mansehra, KPK, Pakistan

    Uzma Khan

  5. Institute of Diet and Nutritional Sciences, The University of Lahore, Islamabad Campus, Islamabad, Pakistan

    Riffat Aysha Anis

  6. Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan

    Mariam Anees & Aneesa Sultan

Authors
  1. Ayesha Ishtiaq
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  2. Tahir Ali
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  3. Attia Bakhtiar
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  4. Robina Bibi
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  5. Kinza Bibi
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  6. Iram Mushtaq
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  7. Shupeng Li
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  8. Wajiha Khan
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  13. Iram Murtaza
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Contributions

Ayesha Ishtiaq (AI), Tahir Ali (TA), Attia Bakhtiar (AB), Robina Bibi (RB), Kinza Bibi (KB), Iram Mushtaq(IM), Shupeng Li (SL), Wajiha Khan (WK), Uzma Khan (UK), Riffat Aysha Anis (RAI), Mariam Anees (MA), Aneesa Sultan (AS), Iram Murtaza (IM*)

AI, TA, RAI, MA, AS, and IM* were involved in the conception and design of the study. AI, TA, AB, RB, KB, IM, SL, WK, UK, and IM* were involved in the data execution and interpretation. AI, TA, AB, RB, KB, IM, SL, WK, UK, MA, AS, and IM* were involved in the investigation and methodology. AI, TA, AB, RB, KB, RAI, MA, AI, and IM* were involved in the roles/writing - original draft; writing. RAI, MA, AS, and IM* were involved in the funding acquisition, supervision, validation, review and editing.

Corresponding author

Correspondence to Iram Murtaza.

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Ethical approval

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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Animal study is involved and relative ethical approval is mentioned ahead.

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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

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