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Modulation of Benzo[a]Pyrene Induced Anxiolytic-Like Behavior by Retinoic Acid in Zebrafish: Involvement of Oxidative Stress and Antioxidant Defense System

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Abstract

Benzo[a]pyrene (B[a]P) is commonly associated with oxidative stress-induced neurotoxicity. Retinoic acid (RA) has been shown to exhibit neuroprotection in brain, and disruption of RA signaling via excess or deficient RA can lead to oxidative stress. B[a]P contamination in aquatic environment has been shown to lower the internal RA level. Thus, the present study was conducted in wild-type zebrafish to ameliorate the neurotoxic effect of B[a]P by waterborne RA co-supplementation. Findings showed that B[a]P induced anxiolytic-like behavioral response, and altered antioxidant activity in zebrafish is attenuated by RA. Our study also advocated the neurotoxic potential of RA treatment alone in control condition. Previous findings showed that periventricular gray zone (PGZ) of optic tectum (TeO) in zebrafish brain regulates anxiety-like behavior. The augmented pyknotic neuronal counts in PGZ following B[a]P treatment was ameliorated by RA co-supplementation. Further, presence of B[a]P in the cell milieu is known to induce oxidative stress through increase expression of cytochrome P450 1A1 (CYP1A1), an enzyme necessary for metabolic breakdown of both B[a]P and RA. Any deviation from the required concentration of RA leads to production of reactive oxygen species. Further, low availability of RA in cell milieu is known to decrease the expression of Nrf2, a transcription factor necessary for the expression of several antioxidants and antioxidant enzymes. Recent studies also showed that RA increases glutathione synthesis and exhibits neuroprotective properties in brain cells. The findings of the present study address the potential role of exogenous RA co-supplementation as a therapeutic intervention against B[a]P-induced depletion of RA, causing neurotoxicity in zebrafish.

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Acknowledgements

The authors acknowledged the financial support provided by the Board of Research in Nuclear Sciences (BRNS), Department of Atomic Energy (DAE), Government of India (sanctioned no. 37(1)/14/27/2015/BRNS). The authors also acknowledged the financial support provided by the Science and Engineering Research Board (SERB), Department of Science and Technology (DST), Government of India (sanctioned no. PDF/2015/000573). The authors also acknowledge the contribution of Mr. Ritendra Mishra, DIHAR, DRDO, who helped in copy editing and proofreading the manuscript.

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  1. Neurobiology Laboratory, Department of Zoology, School of Life Sciences, Ravenshaw University, College Square, Cuttack, Odisha, 753003, India

    Ratnalipi Mohanty, Saroj Kumar Das & Manorama Patri

  2. Department of Biotechnology, School of Life Sciences, Ravenshaw University, Cuttack, Odisha, India

    Ratnalipi Mohanty

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Mohanty, R., Das, S.K. & Patri, M. Modulation of Benzo[a]Pyrene Induced Anxiolytic-Like Behavior by Retinoic Acid in Zebrafish: Involvement of Oxidative Stress and Antioxidant Defense System. Neurotox Res 31, 493–504 (2017). https://doi.org/10.1007/s12640-016-9694-5

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