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Exposure to low-dose arsenic caused teratogenicity and upregulation of proinflammatory cytokines in zebrafish embryos

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Abstract

Arsenic is currently ranked as the most toxicant on the ATSDR 2015 substance priority list and is categorised as a Group 1 human carcinogen. Biota that are subjected to inorganic arsenicals through food, water, occupational or medical exposure pose a risk to the environment and to human health. The present study was carried out to investigate the toxicity caused by inorganic arsenic. After fertilisation, zebrafish embryos were exposed to sodium arsenite at several concentrations (100 nM to 600 nM) for 24 to 96 hpf. The indicators of teratogenicity (hatchability, morphological abnormalities, mortality), behavioural modifications (touch induced escape response (TIER), startle response (SR) and turning behaviour (TB)), biochemical testing (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione S transferase (GST)) and the expressions of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) were investigated. The aforementioned parameters were found to be altered in embryos exposed to sodium arsenite. According to the findings of the current study, even a low dose of inorganic arsenic compound caused teratogenicity, behavioural abnormalities, altered enzyme activities and the expression of proinflammatory cytokines in zebrafish embryos.

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References

  1. Palamuleni LG (2019) Heavy metal pollution in soil and plants from a mining area in the Northwest Province, South Africa (Doctoral dissertation, North-West University (South Africa))

  2. Agency for Toxic Substances and Disease Registry (ATSDR) (2017) Summary data for 2015 priority list of hazardous substances, Agency for Toxic Substances and disease registry. U.S. Division of Toxicology and Human Health Sciences, Atlanta

  3. Naujokas MF, Anderson B, Ahsan H, Aposhian HV, Graziano JH, Thompson C, Suk WA (2013) The broad scope of health effects from chronic arsenic exposure: update on a worldwide public health problem. Environ Health Perspect 121(3):295–302

    Article  PubMed  PubMed Central  Google Scholar 

  4. Thomas DJ, Waters SB, Styblo M (2004) Elucidating the pathway for arsenic methylation. Toxicol Appl Pharmacol 198(3):319–326

    Article  CAS  PubMed  Google Scholar 

  5. Lansdown AB (1995) Physiological and toxicological changes in the skin resulting from the action and interaction of metal ions. Crit Rev Toxicol 25(5):397–462

    Article  CAS  PubMed  Google Scholar 

  6. Jha PK, Tripathi P (2021) Arsenic and fluoride contamination in groundwater: a review of global scenarios with special reference to India. Groundw Sustain Dev 13:100576

    Article  Google Scholar 

  7. Rehman K, Naranmandura H (2012) Arsenic metabolism and thioarsenicals Metallomics 4(9):881–892

    CAS  PubMed  Google Scholar 

  8. Banerjee M, Banerjee N, Bhattacharjee P, Mondal D, Lythgoe PR, Martínez M, Pan J, Polya DA, Giri AK (2013) High arsenic in rice is associated with elevated genotoxic effects in humans. Sci Rep 3(1):1–8

    Article  CAS  Google Scholar 

  9. Abdul KSM, Jayasinghe SS, Chandana EP, Jayasumana C, De Silva PMC (2015) Arsenic and human health effects: a review. Environ Toxicol Pharmacol 40(3):828–846

    Article  PubMed  Google Scholar 

  10. Eddins D, Cerutti D, Williams P, Linney E, Levin ED (2010) Zebrafish provide a sensitive model of persisting neurobehavioral effects of developmental chlorpyrifos exposure: comparison with nicotine and pilocarpine effects and relationship to dopamine deficits. Neurotoxicol Teratol 32(1):99–108

    Article  CAS  PubMed  Google Scholar 

  11. Zanandrea R, Bonan CD and Campos MM (2020) Zebrafish as a model for inflammation and drug discovery, Drug Discovery Today. https://doi.org/10.1016/j.drudis.2020.09.036

  12. Busquet F, Strecker R, Rawlings JM, Belanger SE, Braunbeck T, Carr GJ, Cenijn P, Fochtman P, Gourmelon A, Hübler N, Kleensang A (2014) OECD validation study to assess intra-and inter-laboratory reproducibility of the zebrafish embryo toxicity test for acute aquatic toxicity testing. Regul Toxicol Pharmacol 69(3):496–511

    Article  CAS  PubMed  Google Scholar 

  13. Truong L, Tanguay RL (2017) Evaluation of embryotoxicity using the zebrafish model. Methods Mol Biol 1641:325–333. https://doi.org/10.1007/978-1-4939-7172-5_18

    Article  CAS  PubMed  Google Scholar 

  14. Lahnsteiner F (2008) The sensitivity and reproducibility of the zebrafish (Danio rerio) embryo test for the screening of wastewater quality and for testing the toxicity of chemicals. ATLA Altern Lab Anim 36(3):299–311. https://doi.org/10.1177/026119290803600308

    Article  CAS  PubMed  Google Scholar 

  15. Embry MR, Belanger SE, Braunbeck TA, Galay-Burgos M, Halder M, Hinton DE, Léonard MA, Lillicrap A, Norberg-King T, Whale G (2010) The fish embryo toxicity test as an animal alternative method in hazard and risk assessment and scientific research. Aquat Toxicol 97(2):79–87

    Article  CAS  PubMed  Google Scholar 

  16. Del Razo LM, Quintanilla-Vega B, Brambila-Colombres E, Calderón-Aranda ES, Manno M, Albores A (2001) Stress proteins induced by arsenic. Toxicol Appl Pharmacol 177(2):132–148

    Article  PubMed  Google Scholar 

  17. Xing P, Zhang Y, Chi Q, Li S (2022) Zinc alleviates arsenic-induced inflammation and apoptosis in the head kidney of common carp by inhibiting oxidative stress and endoplasmic reticulum stress. Biol Trace Elem Res 200(5):2380–2390

    Article  CAS  PubMed  Google Scholar 

  18. Milan FS, Maleki BRS, Moosavy MH, Mousavi S, Sheikhzadeh N, Khatibi SA (2021) Ameliorating effects of dietary Haematococcus pluvialis on arsenic-induced oxidative stress in rainbow trout (Oncorhynchus mykiss) fillet. Ecotoxicol Environ Saf 207:111559

    Article  CAS  PubMed  Google Scholar 

  19. Allen T, Rana SVS (2004) Effect of arsenic (AsIII) on glutathione-dependent enzymes in liver and kidney of the freshwater fish Channa punctatus. Biol Trace Elem Res 100(1):39–48

    Article  CAS  PubMed  Google Scholar 

  20. González Núñez AA, Ferro JP, Campos LB, Eissa BL, Mastrángelo MM, Ferrari L, Ossana NA (2022) Evaluation of the acute effects of arsenic on adults of the neotropical native fish Cnesterodon decemmaculatus using a set of biomarkers. Environ Toxicol Chem 41(5):1246–1259

    Article  PubMed  Google Scholar 

  21. Barone G, Storelli A, Garofalo R, Mallamaci R, Storelli MM (2022) Residual levels of mercury, cadmium, lead and arsenic in some commercially key species from Italian Coasts (Adriatic Sea): Focus on Human Health. Toxics 10(5):223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Wang T, Secombes CJ (2009) Identification and expression analysis of two fish-specific IL-6 cytokine family members, the ciliary neurotrophic factor (CNTF)-like and M17 genes, in rainbow trout Oncorhynchus mykiss. Mol Immunol 46(11–12):2290–2298

    Article  CAS  PubMed  Google Scholar 

  23. Secombes CJ, Zou J, Bird S (2009) Fish cytokines: discovery, activities and potential applications. Fish Defenses 1:1–36

    Google Scholar 

  24. Laing KJ, Secombes CJ (2004) Chemokines. Dev Comp Immunol 28(5):443–460

    Article  CAS  PubMed  Google Scholar 

  25. Aleström P, D’Angelo L, Midtlyng PJ, Schorderet DF, Schulte-Merker S, Sohm F, Warner S (2020) Zebrafish: housing and husbandry recommendations. Lab Anim 54(3):213–224

    Article  PubMed  Google Scholar 

  26. Ali S, Van Mil HG, Richardson MK (2011) Large-scale assessment of the zebrafish embryo as a possible predictive model in toxicity testing. PLoS ONE 6(6):e21076

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Gilbert BM, Avenant-Oldewage A (2016) Hatchability and survival of oncomiracidia of Paradiplozoon ichthyoxanthon (Monogenea: Diplozoidae) exposed to aqueous aluminium. Parasit Vectors 9(1):1–11

    Article  Google Scholar 

  28. Kong X, Jiang H, Wang S, Wu X, Fei W, Li L, Nie G, Li X (2013) Effects of copper exposure on the hatching status and antioxidant defense at different developmental stages of embryos and larvae of goldfish Carassius auratus. Chemosphere 92(11):1458–1464

    Article  CAS  PubMed  Google Scholar 

  29. Aksakal FI, Ciltas A (2019) Impact of copper oxide nanoparticles (CuO NPs) exposure on embryo development and expression of genes related to the innate immune system of zebrafish (Danio rerio). Comp Biochem Physiol C: Toxicol Pharmacol 223:78–87a

    CAS  PubMed  Google Scholar 

  30. Coral JA, Heaps S, Glaholt SP, Karty JA, Jacobson SC, Shaw JR, Bondesson M (2021) Arsenic exposure induces a bimodal toxicity response in zebrafish. Environ Pollut 287:117637

    Article  CAS  PubMed  Google Scholar 

  31. Misra HP, Fridovich I (1972) The generation of superoxide radical during the autoxidation of hemoglobin. J Biol Chem 247(21):6960–6962

    Article  CAS  PubMed  Google Scholar 

  32. Sinha AK (1972) Colorimetric assay of catalase. Anal Biochem 47(2):389–394

    Article  CAS  PubMed  Google Scholar 

  33. Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra W (1973) Selenium: biochemical role as a component of glutathione peroxidase. Science 179(4073):588–590

    Article  CAS  PubMed  Google Scholar 

  34. Habig WH and Jakoby WB (1981) [51]Assays for differentiation of glutathione S-transferases. In Methods in enzymology 77:398–405. Academic press

  35. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72(1–2):248–254

    Article  CAS  PubMed  Google Scholar 

  36. Livak KJ and Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods 25(4):402–408

  37. Laemmli UK, Beguin F, Gujer-Kellenberger G (1970) A factor preventing the major head protein of bacteriophage T4 from random aggregation. J Mol Biol 47(1):69–85

    Article  CAS  PubMed  Google Scholar 

  38. Kabir T, Anwar S, Mourosi JT, Hossain J, Rabbane MG, Rahman MM, Tahsin T, Hasan MN, Shill MC, Hosen MJ (2020) Arsenic hampered embryonic development: an in vivo study using local Bangladeshi Danio rerio model. Toxicol Rep 7:155–161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Li D, Lu C, Wang J, Hu W, Cao Z, Sun D, Xia H, Ma X (2009) Developmental mechanisms of arsenite toxicity in zebrafish (Danio rerio) embryos. Aquat Toxicol 91(3):229–237

    Article  CAS  PubMed  Google Scholar 

  40. Fuse Y, Nguyen VT, Kobayashi M (2016) Nrf2-dependent protection against acute sodium arsenite toxicity in zebrafish. Toxicol Appl Pharmacol 305:136–142

    Article  CAS  PubMed  Google Scholar 

  41. Olivares CI, Field JA, Simonich M, Tanguay RL, Sierra-Alvarez R (2016) Arsenic (III, V), indium (III), and gallium (III) toxicity to zebrafish embryos using a high-throughput multi-endpoint in vivo developmental and behavioral assay. Chemosphere 148:361–368

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Sun HJ, Xiang P, Tang MH, Sun L, Ma LQ (2016) Arsenic impacted the development, thyroid hormone and gene transcription of thyroid hormone receptors in bighead carp larvae (Hypophthalmichthys nobilis). J Hazard Mater 303:76–82

    Article  CAS  PubMed  Google Scholar 

  43. Zikic V, Stajn AS, Ognjanovic BI, Pavlovic SZ, Saicic ZS (1997) Activities of superoxide dismutase and catalase in erythrocytes and transaminases in the plasma of carps (Cyprinus carpio L.) expose to cadmium. Physiol Res 46:391–396

    CAS  PubMed  Google Scholar 

  44. Farombi EO, Adelowo OA, Ajimoko YR (2007) Biomarkers of oxidative stress and heavy metal levels as indicators of environmental pollution in African catfish (Clarias gariepinus) from Nigeria Ogun River. Int J Environ Res Public Health 4(2):158–165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Di Giulio RT, Washburn PC, Wenning RJ, Winston GW, Jewell CS (1989) Biochemical responses in aquatic animals: a review of determinants of oxidative stress. Environ Toxicol Chem: An Int J 8(12):1103–1123

    Article  Google Scholar 

  46. Sun HJ, Zhao WJ, Teng XQ, Shu SP, Li SW, Hong HC, Guan DX (2020) Antioxidant responses and pathological changes in the gill of zebrafish (Danio rerio) after chronic exposure to arsenite at its reference dose. Ecotoxicol Environ Saf 200:110743

    Article  CAS  PubMed  Google Scholar 

  47. Kim JH, Kang JC (2015) The arsenic accumulation and its effect on oxidative stress responses in juvenile rockfish, Sebastes schlegelii, exposed to waterborne arsenic (As3+). Environ Toxicol Pharmacol 39(2):668–676

    Article  CAS  PubMed  Google Scholar 

  48. Flora SJ (2011) Arsenic-induced oxidative stress and its reversibility. Free Radical Biol Med 51(2):257–281

    Article  CAS  Google Scholar 

  49. Thompson JA, White CC, Cox DP, Chan JY, Kavanagh TJ, Fausto N, Franklin CC (2009) Distinct Nrf1/2-independent mechanisms mediate As3+-induced glutamate-cysteine ligase subunit gene expression in murine hepatocytes. Free Radical Biol Med 46(12):1614–1625

    Article  CAS  Google Scholar 

  50. Aruljothi B and Samipillai SS (2014) Effect of arsenic on lipid peroxidation and antioxidants system in freshwater fish. Labeo roh Greani S, Lourkisti R, Berti L, Marchand B, Giannettini J, Santini J and Quilichini Y (2017) Effect of chronic arsenic exposure under environmental conditions on bioaccumulation, oxidative stress, and antioxidant enzymatic defenses in wild trout Salmo trutta (Pisces, Teleostei). Ecotoxicology 26(7):930–941

  51. Greani S, Lourkisti R, Berti L, Marchand B, Giannettini J, Santini J, Quilichini Y (2017) Effect of chronic arsenic exposure under environmental conditions on bioaccumulation, oxidative stress, and antioxidant enzymatic defenses in wild trout Salmo trutta (Pisces, Teleostei). Ecotoxicology 26(7):930–941

    Article  CAS  PubMed  Google Scholar 

  52. Leite CE (2013) Caracterização de um modelo de inflamação em larvas de zebrafish: o papel do sistema purinérgico

  53. Kozul CD, Hampton TH, Davey JC, Gosse JA, Nomikos AP, Eisenhauer PL, Weiss DJ, Thorpe JE, Ihnat MA, Hamilton JW (2009) Chronic exposure to arsenic in the drinking water alters the expression of immune response genes in mouse lung. Environ Health Perspect 117(7):1108–1115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

Tamil Nadu Dr. J. Jayalalithaa Fisheries University – Institute of Fisheries Postgraduate Studies provided the funds and all the necessary facilities to carry out this study.

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Authors

Contributions

Modi Kiran — performed experiment and drafted the article, prepared the figures and tables.

Ambika Binesh — designed the experiment and reviewed the manuscript.

S. A. Shanmugam — reviewed the manuscript.

Kaliyamurthi Venkatachalam — designed the experiment, drafted and edited the manuscript.

Corresponding author

Correspondence to Kaliyamurthi Venkatachalam.

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The authors declare no competing interests.

Ethical Statement

Zebrafish were maintained as per Institutional Animal Ethical Care (IAEC) and committee for the purpose of control and supervision of experiments on animals (CPCSEA).

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The authors declare no competing interests.

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Piyushbhai, M.K., Binesh, A., Shanmugam, S.A. et al. Exposure to low-dose arsenic caused teratogenicity and upregulation of proinflammatory cytokines in zebrafish embryos. Biol Trace Elem Res 201, 3487–3496 (2023). https://doi.org/10.1007/s12011-022-03418-w

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