title: Modulation of Benzo[a]Pyrene Induced Anxiolytic-Like Behavior by Retinoic Acid in Zebrafish: Involvement of Oxidative Stress and Antioxidant Defense System.
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.
authors.affiliation: Neurobiology Laboratory, Department of Zoology, School of Life Sciences, Ravenshaw University, College Square, Cuttack, Odisha, 753003, India.|Department of Biotechnology, School of Life Sciences, Ravenshaw University, Cuttack, Odisha, India.
authors.forename: Ratnalipi
authors.initials: R
authors.lastname: Mohanty
authors.affiliation: Neurobiology Laboratory, Department of Zoology, School of Life Sciences, Ravenshaw University, College Square, Cuttack, Odisha, 753003, India.
authors.forename: Saroj Kumar
authors.initials: SK
authors.lastname: Das
authors.affiliation: Neurobiology Laboratory, Department of Zoology, School of Life Sciences, Ravenshaw University, College Square, Cuttack, Odisha, 753003, India. mpatri@ravenshawuniversity.ac.in.
authors.forename: Manorama
authors.initials: M
authors.lastname: Patri
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000633:toxicity; D000975:Antioxidants / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001564:Benzo(a)pyrene / Q000037:antagonists & inhibitors* / Q000633:toxicity; D001921:Brain / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D050050:Protein Carbonylation / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*; D015027:Zebrafish
chemical_list: D014151:Anti-Anxiety Agents; D000975:Antioxidants; D018696:Neuroprotective Agents; D001564:Benzo(a)pyrene; D014212:Tretinoin; D002374:Catalase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione
keywords: Behavior; Benzo[a]pyrene (B[a]P); Neuroprotection; Neurotoxicity; Oxidative stress; Retinoic acid (RA)