title: Fluoride exposure abates pro-inflammatory response and induces in vivo apoptosis rendering zebrafish (Danio rerio) susceptible to bacterial infections.
abstract: The present study describes the immunotoxic effect of chronic fluoride exposure on adult zebrafish (Danio rerio). Zebrafish were exposed to fluoride (71.12 mg/L; 1/10 LC50) for 30 d and the expression of selected genes studied. We observed significant elevation in the detoxification pathway gene cyp1a suggesting chronic exposure to non-lethal concentration of fluoride is indeed toxic to fish. Fluoride mediated pro-oxidative stress is implicated with the downregulation in superoxide dismutase 1 and 2 (sod1/2) genes. Fluoride affected DNA repair machinery by abrogating the expression of the DNA repair gene rad51 and growth arrest and DNA damage inducible beta a gene gadd45ba. The upregulated expression of casp3a coupled with altered Bcl-2 associated X protein/B-cell lymphoma 2 ratio (baxa/bcl2a) clearly suggested chronic fluoride exposure induced the apoptotic cascade in zebrafish. Fluoride-exposed zebrafish when challenged with non-lethal dose of fish pathogen A. hydrophila revealed gross histopathology in spleen, bacterial persistence and significant mortality. We report that fluoride interferes with system-level output of pro-inflammatory cytokines tumour necrosis factor-α, interleukin-1β and interferon-γ, as a consequence, bacteria replicate efficiently causing significant fish mortality. We conclude, chronic fluoride exposure impairs the redox balance, affects DNA repair machinery with pro-apoptotic implications and suppresses pro-inflammatory cytokines expression abrogating host immunity to bacterial infections.
authors.affiliation: Immunobiology Laboratory, Department of Zoology, University of Delhi, Delhi 110 007, India.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Singh
authors.affiliation: Immunobiology Laboratory, Department of Zoology, University of Delhi, Delhi 110 007, India.
authors.forename: Preeti
authors.initials: P
authors.lastname: Khatri
authors.affiliation: Immunobiology Laboratory, Department of Zoology, University of Delhi, Delhi 110 007, India.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Srivastava
authors.affiliation: Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi 110007, India.
authors.forename: Shruti
authors.initials: S
authors.lastname: Jain
authors.affiliation: Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi 110007, India.
authors.forename: Vani
authors.initials: V
authors.lastname: Brahmachari
authors.affiliation: National Institute of Cholera and Enteric Diseases, Kolkata, West Bengal 700010, India.
authors.forename: Asish
authors.initials: A
authors.lastname: Mukhopadhyay
authors.affiliation: Immunobiology Laboratory, Department of Zoology, University of Delhi, Delhi 110 007, India. Electronic address: shibnath1@yahoo.co.in.
authors.forename: Shibnath
authors.initials: S
authors.lastname: Mazumder
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair / Q000187:drug effects*; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism; D005459:Fluorides / Q000276:immunology / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000276:immunology / Q000633:toxicity*; D015027:Zebrafish / Q000276:immunology*
chemical_list: D000975:Antioxidants; D016207:Cytokines; D029941:Fish Proteins; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D014874:Water Pollutants, Chemical; D007371:Interferon-gamma; D005459:Fluorides
keywords: Apoptosis; DNA repair; Fluoride; Oxidative stress; Pro-inflammatory cytokine; Zebrafish