title: Differential modulation of cellular antioxidant status in zebrafish liver and kidney exposed to low dose arsenic trioxide.
abstract: Zebrafish were exposed to a nonlethal dose (1/350LC50; 50µg/L) of As2O3and sampled at 7, 15, 30, 60 and 90 days of treatment. The oxidative stress response was assessed in terms of time-dependent histopathological changes, lipid peroxidation, GSH status, activities of detoxification enzymes and expression of antioxidant genes in liver and kidney. As2O3treatment enhanced lipid peroxidation except at day 90 in liver and day 30 in kidney. Glutathione depleted significantly in the liver except on day 30; whereas in kidney, it increased initially but thereafter depleted significantly. The liver GST activity was high until day 30, low on day 60 and high on day 90. On the other hand, activity of GST in kidney remained high throughout the exposure. GR activity in liver decreased initially but augmented from 30 days onwards whereas in kidney it remained high until 30 days of exposure. Significant increase in GPx and CAT activities in liver and kidney confirmed oxidative stress in zebrafish which correlated with mRNA expression of antioxidant genes. Upregulation in mRNA level of Cu-Zn Sod in liver and kidney was prominent. Gpx1 upregulation was more conspicuous in kidney as compared to liver while the pattern of Cat expression was almost similar in both the organs. Among the mitochondrial genes, expression of Cox1 was significantly high only after 90 days in liver, while in kidney it enhanced at 7, 30 and 60 days of arsenic exposure. Ucp2 was upregulated in liver after 15 days of exposure but significantly downregulated at day 90; in kidney it remained unchanged at other time points except at day 90. An overall increased expression of Bcl2 further confirmed As2O3induced oxidative stress in zebrafish liver and kidney. The pattern of mRNA expression of Nrf2 was not uniform and was in accordance to its downstream antioxidant genes. Present findings elucidate that low dose of As2O3exposure induces a time dependent differential modulation of antioxidant status in liver and kidney of zebrafish in a tissue-specific manner.
authors.affiliation: Environmental Toxicology Laboratory, Department of Zoology, School of Life Sciences, Visva-Bharati University, Santiniketan, West Bengal 731235, India.
authors.forename: Shuvasree
authors.initials: S
authors.lastname: Sarkar
authors.affiliation: Environmental Toxicology Laboratory, Department of Zoology, School of Life Sciences, Visva-Bharati University, Santiniketan, West Bengal 731235, India.
authors.forename: Sandip
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Molecular Genetics Laboratory, Department of Zoology, School of Life Sciences, Visva-Bharati University, Santiniketan, West Bengal 731235, India.
authors.forename: Ansuman
authors.initials: A
authors.lastname: Chattopadhyay
authors.affiliation: Environmental Toxicology Laboratory, Department of Zoology, School of Life Sciences, Visva-Bharati University, Santiniketan, West Bengal 731235, India. Electronic address: shelleyb38@gmail.com.
authors.forename: Shelley
authors.initials: S
authors.lastname: Bhattacharya
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage; D002374:Catalase / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000235:genetics; D005260:Female; D050259:Genes, Mitochondrial; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007668:Kidney / Q000201:enzymology* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress; D010087:Oxides / Q000008:administration & dosage / Q000633:toxicity*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D000071246:Uncoupling Protein 2 / Q000235:genetics; D015854:Up-Regulation; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1
chemical_list: D000975:Antioxidants; D001152:Arsenicals; D051267:NF-E2-Related Factor 2; D010087:Oxides; D019253:Proto-Oncogene Proteins c-bcl-2; D000071246:Uncoupling Protein 2; D029961:Zebrafish Proteins; C495638:nfe2l2a protein, zebrafish; D002374:Catalase; D005979:Glutathione Peroxidase; D051545:Cyclooxygenase 1; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione; D000077237:Arsenic Trioxide; D000094765:Glutathione Peroxidase GPX1
keywords: Antioxidant genes; Arsenic trioxide; Histopathology; Kidney; Liver; Oxidative stress