Advertisement

Zebrafish as a Vertebrate Model to Assess Sublethal Effects and Health Risks of Emerging Pollutants

  • Demetrio Raldúa
  • Carlos Barata
  • Marta Casado
  • Melissa Faria
  • José María Navas
  • Alba Olivares
  • Eva Oliveira
  • Sergi Pelayo
  • Benedicte Thienpont
  • Benjamin PiñaEmail author
Chapter
  • 3.2k Downloads
Part of the The Handbook of Environmental Chemistry book series (HEC, volume 20)

Abstract

Zebrafish is developing as a major model for assessing toxicity of pharmaceuticals, drugs, and pollutants. Besides its applications in regulatory toxicity and drug discovery, its characteristics make it a unique system to analyze sublethal toxic effects that only can be studied applying holistic, in toto approaches. Here, we show some of these analyses, in which complex organic systems (neuronal, muscular, sensorial, digestive, thyroid), as well as the embryonic development, show specific effects upon exposure to pharmaceuticals and several environmentally relevant substances, including nanoparticles and other emerging pollutants for which no adequate toxicological profile is still available. These analyses are especially relevant for embryo risk evaluation, given the close similarity of the early stages of the development in all vertebrates, including humans.

Keywords

Dioxins Environmental Pollution Nanoparticles Neurotoxicity Thyroid disrupters 

Notes

Acknowledgments

This work was supported by the Spanish Ministry of Science and Innovation (grants CGL2008-01898/BOS and CTM2011-30471-C02-01), the INIA (grant RTA2009-00074-00-00), the Generalitat de Catalunya (grant 2009 SGR 924) and European Union (FP7 EU Project Managing the Risks of Nanomaterials-MARINA). E.O. acknowledges a predoctoral fellowship from the Portuguese Fundação para a Ciência e Tecnologia (SFRH/BD/48244/2008). B.T. acknowledges a predoctoral fellowship from the Spanish Ministry of Science and Innovation (FPU AP2006-01324).

References

  1. 1.
    Love DR, Pichler FB, Dodd A, Copp BR, Greenwood DR (2004) Technology for high-throughput screens: the present and future using zebrafish. Curr Opin Biotechnol 15:564–571CrossRefGoogle Scholar
  2. 2.
    Goldsmith P (2004) Zebrafish as a pharmacological tool: the how, why and when. Curr Opin Pharmacol 4:504–512CrossRefGoogle Scholar
  3. 3.
    McGrath P, Li CQ (2008) Zebrafish: a predictive model for assessing drug-induced toxicity. Drug Discov Today 13:394–401CrossRefGoogle Scholar
  4. 4.
    Zon L, Peterson R (2005) In vivo drug discovery in the zebrafish. Nat Rev Drug Discov 4:35–44CrossRefGoogle Scholar
  5. 5.
    Berghmans S, Butler P, Goldsmith P, Waldron G, Gardner I, Golder Z, Richards FM, Kimber G, Roach A, Alderton W, Fleming A (2008) Zebrafish based assays for the assessment of cardiac, visual and gut function–potential safety screens for early drug discovery. J Pharmacol Toxicol Methods 58:59–68CrossRefGoogle Scholar
  6. 6.
    Langheinrich U (2003) Zebrafish: a new model on the pharmaceutical catwalk. Bioessays 25:904–912CrossRefGoogle Scholar
  7. 7.
    Parng C, Roy NM, Ton C, Lin Y, McGrath P (2007) Neurotoxicity assessment using zebrafish. J Pharmacol Toxicol Methods 55:103–112CrossRefGoogle Scholar
  8. 8.
    Ton C, Lin Y, Willett C (2006) Zebrafish as a model for developmental neurotoxicity testing. Birth Defects Res A Clin Mol Teratol 76:553–567CrossRefGoogle Scholar
  9. 9.
    Chen Q, Huang NN, Huang JT, Chen S, Fan J, Li C, Xie FK (2009) Sodium benzoate exposure downregulates the expression of tyrosine hydroxylase and dopamine transporter in dopaminergic neurons in developing zebrafish. Birth Defects Res B Dev Reprod Toxicol 86:85–91CrossRefGoogle Scholar
  10. 10.
    Wen L, Wei W, Gu W, Huang P, Ren X, Zhang Z, Zhu Z, Lin S, Zhang B (2008) Visualization of monoaminergic neurons and neurotoxicity of MPTP in live transgenic zebrafish. Dev Biol 314:84–92CrossRefGoogle Scholar
  11. 11.
    Rubinstein AL (2006) Zebrafish assays for drug toxicity screening. Expert Opin Drug Metab Toxicol 2:231–240CrossRefGoogle Scholar
  12. 12.
    Froehlicher M, Liedtke A, Groh KJ, Neuhauss SC, Segner H, Eggen RI (2009) Zebrafish (Danio rerio) neuromast: promising biological endpoint linking developmental and toxicological studies. Aquat Toxicol 95:307–319CrossRefGoogle Scholar
  13. 13.
    Bricaud O, Chaar V, Dambly-Chaudiere C, Ghysen A (2001) Early efferent innervation of the zebrafish lateral line. J Comp Neurol 434:253–261CrossRefGoogle Scholar
  14. 14.
    Yang L, Kemadjou J, Zinsmeister C, Bauer M, Legradi J, Muller F, Pankratz M, Jakel J, Strahle U (2007) Transcriptional profiling reveals barcode-like toxicogenomic responses in the zebrafish embryo. Genome Biol 8:R227CrossRefGoogle Scholar
  15. 15.
    Chiu LL, Cunningham LL, Raible DW, Rubel EW, Ou HC (2008) Using the zebrafish lateral line to screen for ototoxicity. J Assoc Res Otolaryngol 9:178–190CrossRefGoogle Scholar
  16. 16.
    Seiler C, Nicolson T (1999) Defective calmodulin-dependent rapid apical endocytosis in zebrafish sensory hair cell mutants. J Neurobiol 41:424–434CrossRefGoogle Scholar
  17. 17.
    Ton C, Parng C (2005) The use of zebrafish for assessing ototoxic and otoprotective agents. Hear Res 208:79–88CrossRefGoogle Scholar
  18. 18.
    Chow ESH, Cheng SH (2003) Cadmium affects muscle type development and axon growth in zebrafish embryonic somitogenesis. Toxicol Sci 73:149–159CrossRefGoogle Scholar
  19. 19.
    Sylvain NJ, Brewster DL, Ali DW (2010) Zebrafish embryos exposed to alcohol undergo abnormal development of motor neurons and muscle fibers. Neurotoxicol Teratol 32:472–480CrossRefGoogle Scholar
  20. 20.
    Tilton F, Tanguay RL (2008) Exposure to sodium metam during zebrafish somitogenesis results in early transcriptional indicators of the ensuing neuronal and muscular dysfunction. Toxicol Sci 106:103–112CrossRefGoogle Scholar
  21. 21.
    Tsay HJ, Wang YH, Chen WL, Huang MY, Chen YH (2007) Treatment with sodium benzoate leads to malformation of zebrafish larvae. Neurotoxicol Teratol 29:562–569CrossRefGoogle Scholar
  22. 22.
    Bruses JL (2011) N-cadherin regulates primary motor axon growth and branching during zebrafish embryonic development. J Comp Neurol 519:1797–1815CrossRefGoogle Scholar
  23. 23.
    Kanungo J, Zheng YL, Amin ND, Kaur S, Ramchandran R, Pant HC (2009) Specific inhibition of cyclin-dependent kinase 5 activity induces motor neuron development in vivo. Biochem Biophys Res Commun 386:263–267CrossRefGoogle Scholar
  24. 24.
    Raldua D, Andre M, Babin PJ (2008) Clofibrate and gemfibrozil induce an embryonic malabsorption syndrome in zebrafish. Toxicol Appl Pharmacol 228:301–314CrossRefGoogle Scholar
  25. 25.
    Chen YH, Huang YH, Wen CC, Wang YH, Chen WL, Chen LC, Tsay HJ (2008) Movement disorder and neuromuscular change in zebrafish embryos after exposure to caffeine. Neurotoxicol Teratol 30:440–447CrossRefGoogle Scholar
  26. 26.
    Cao P, Hanai J, Tanksale P, Imamura S, Sukhatme VP, Lecker SH (2009) Statin-induced muscle damage and atrogin-1 induction is the result of a geranylgeranylation defect. FASEB J 23:2844–2854CrossRefGoogle Scholar
  27. 27.
    Stehr CM, Linbo TL, Incardona JP, Scholz NL (2006) The developmental neurotoxicity of fipronil: notochord degeneration and locomotor defects in zebrafish embryos and larvae. Toxicol Sci 92:270–278CrossRefGoogle Scholar
  28. 28.
    Lambrechts D, Carmeliet P (2004) Genetics in zebrafish, mice, and humans to dissect congenital heart disease: insights in the role of VEGF. Curr. Topics in Develop. Biol. 62:189–224CrossRefGoogle Scholar
  29. 29.
    Stainier DYR (2001) Zebrafish genetics and vertebrate heart formation. Nat Rev Genet 2:39–48CrossRefGoogle Scholar
  30. 30.
    Cole P, Trichopoulos D, Pastides H, Starr T, Mandel JS (2003) Dioxin and cancer: a critical review. Regul Toxicol Pharmacol 38:378–388CrossRefGoogle Scholar
  31. 31.
    Antkiewicz DS, Burns CG, Carney SA, Peterson RE, Heideman W (2005) Heart malformation is an early response to TCDD in embryonic zebrafish. Toxicol Sci 84:368–377CrossRefGoogle Scholar
  32. 32.
    Antkiewicz DS, Peterson RE, Heideman W (2006) Blocking expression of AHR2 and ARNT1 in zebrafish larvae protects against cardiac toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Sci 94:175–182CrossRefGoogle Scholar
  33. 33.
    Belair CD, Peterson RE, Heideman W (2001) Disruption of erythropoiesis by dioxin in the zebrafish. Dev Dyn 222:581–594CrossRefGoogle Scholar
  34. 34.
    Bello SM, Heideman W, Peterson RE (2004) 2,3,7,8-Tetrachlorodibenzo-p-dioxin inhibits regression of the common cardinal vein in developing zebrafish. Toxicol Sci 78:258–266CrossRefGoogle Scholar
  35. 35.
    Gonzalez FJ, Fernández-Salguero P (1998) The aryl hydrocarbon receptor: studies using the AHR-null mice. Drug Metab Dispos 26:1194–1198Google Scholar
  36. 36.
    Hankinson O (1995) The aryl hydrocarbon receptor complex. Annu Rev Pharmacol Toxicol 35:307–340CrossRefGoogle Scholar
  37. 37.
    Nebert DW, Puga A, Vasiliou V (1993) Role of the Ah receptor and the dioxin-inducible [Ah] gene battery in toxicity, cancer, and signal transduction. Ann N Y Acad Sci 685:624–640CrossRefGoogle Scholar
  38. 38.
    Shimizu Y, Nakatsuru Y, Ichinose M, Takahashi Y, Kume H, Mimura J, Fujii-Kuriyama Y, Ishikawa T (2000) Benzo[a]pyrene carcinogenicity is lost in mice lacking the aryl hydrocarbon receptor. Proc Natl Acad Sci USA 97:779–782CrossRefGoogle Scholar
  39. 39.
    Prasch AL, Tanguay RL, Mehta V, Heideman W, Peterson RE (2006) Identification of zebrafish ARNT1 homologs: 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity in the developing zebrafish requires ARNT1. Mol Pharmacol 69:776–787Google Scholar
  40. 40.
    Prasch AL, Teraoka H, Carney SA, Dong W, Hiraga T, Stegeman JJ, Heideman W, Peterson RE (2003) Aryl hydrocarbon receptor 2 mediates 2,3,7,8-tetrachlorodibenzo-p-dioxin developmental toxicity in zebrafish. Toxicol Sci 76:138–150CrossRefGoogle Scholar
  41. 41.
    Carney S, Prasch A, Heideman W, Peterson R (2006) Understanding dioxin developmental toxicity using the zebrafish model. Birth Defects Res A Clin Mol Teratol 76:7–18CrossRefGoogle Scholar
  42. 42.
    Prasch AL, Heideman W, Peterson RE (2004) ARNT2 is not required for TCDD developmental toxicity in zebrafish. Toxicol Sci 82:250–258CrossRefGoogle Scholar
  43. 43.
    Scott JA, Incardona JP, Pelkki K, Shepardson S, Hodson PV (2011) AhR2-mediated, CYP1A-independent cardiovascular toxicity in zebrafish (Danio rerio) embryos exposed to retene. Aquat Toxicol 101:165–174CrossRefGoogle Scholar
  44. 44.
    Scholz S, Mayer I (2008) Molecular biomarkers of endocrine disruption in small model fish. Mol Cell Endocrinol 293:57–70CrossRefGoogle Scholar
  45. 45.
    DeVito M, Biegel L, Brouwer A, Brown S, Brucker-Davis F, Cheek AO, Christensen R, Colborn T, Cooke P, Crissman J, Crofton K, Doerge D, Gray E, Hauser P, Hurley P, Kohn M, Lazar J, McMaster S, McClain M, McConnell E, Meier C, Miller R, Tietge J, Tyl R (1999) Screening methods for thyroid hormone disruptors. Environ Health Perspect 107:407–415CrossRefGoogle Scholar
  46. 46.
    OECD (2006) Detailed review paper on thyroid hormone disruption assays. OECD series on testing and assessment. OECD, ParisGoogle Scholar
  47. 47.
    Brent GA, Braverman LE, Zoeller RT (2007) Thyroid health and the environment. Thyroid 17:807–809CrossRefGoogle Scholar
  48. 48.
    Crofton KM (2008) Thyroid disrupting chemicals: mechanisms and mixtures. Int J Androl 31:209–223CrossRefGoogle Scholar
  49. 49.
    Raldúa D, Babin PJ (2009) Simple, rapid zebrafish larva bioassay for assessing the potential of chemical pollutants and drugs to disrupt thyroid gland function. Environ Sci Technol 43:6844–6850CrossRefGoogle Scholar
  50. 50.
    Alt B, Reibe S, Feitosa NM, Elsalini OA, Wendl T, Rohr KB (2006) Analysis of origin and growth of the thyroid gland in zebrafish. Dev Dyn 235:1872–1883CrossRefGoogle Scholar
  51. 51.
    Brown DD (1997) The role of thyroid hormone in zebrafish and axolot development. Proc Natl Acad Sci USA 94:13011–13016CrossRefGoogle Scholar
  52. 52.
    Walpita CN, Crawford AD, Janssens EDR, Van der Geyten S, Darras VM (2009) Type 2 iodothyronine deiodinase Is essential for thyroid hormone-dependent embryonic development and pigmentation in zebrafish. Endocrinology 150:530–539CrossRefGoogle Scholar
  53. 53.
    Parichy DM, Tumer JM (2003) Zebrafish puma mutant decouples pigment pattern and somatic metamorphosis. Dev Biol 256:242–257CrossRefGoogle Scholar
  54. 54.
    Allison WT, Dann SG, Veldhoen KM, Hawryshyn CW (2006) Degeneration and regeneration of ultraviolet cone photoreceptors during development in rainbow trout. J Comp Neurol 499:702–715CrossRefGoogle Scholar
  55. 55.
    Benbassat J (1974) The transition from tadpole to frog haemoglobin during natural amphibian metamorphosis. I. Protein synthesis by peripheral blood cells in vitro. J Cell Sci 15:347–357Google Scholar
  56. 56.
    Opitz R, Braunbeck T, Bogi C, Pickford DB, Nentwig G, Oehlmann J, Tooi O, Lutz I, Kloas W (2005) Description and initial evaluation of a xenopus metamorphosis assay for detection of thyroid system-disrupting activities of environmental compounds. Environ Toxicol Chem 24:653–664CrossRefGoogle Scholar
  57. 57.
    Solbakken JS, Norberg B, Watanabe K, Pittman K (1999) Thyroxine as a mediator of metamorphosis of Atlantic halibut, Hippoglossus hippoglossus. Environ Biol Fishes 56:53–65CrossRefGoogle Scholar
  58. 58.
    Tata JR (2006) Amphibian metamorphosis as a model for the developmental actions of thyroid hormone. Mol Cell Endocrinol 246:10–20CrossRefGoogle Scholar
  59. 59.
    Temple SE, Ramsden SD, Haimberger TJ, Veldhoen KM, Veldhoen NJ, Carter NL, Roth WM, Hawryshyn CW (2008) Effects of exogenous thyroid hormones on visual pigment composition in coho salmon (Oncorhynchus kisutch). J Exp Biol 211:2134–2143CrossRefGoogle Scholar
  60. 60.
    Youson JH, Manzon RG, Peck BJ, Holmes JA (1997) Effects of exogenous thyroxine (T4) and triiodothyronine (T3) on spontaneous metamorphosis and serum T4 and T3 levels in immediately premetamorphic sea lampreys, Petromyzon marinus. J Exp Zool 279:145–155CrossRefGoogle Scholar
  61. 61.
    Barros TP, Alderton WK, Reynolds HM, Roach AG, Berghmans S (2008) Zebrafish: an emerging technology for in vivo pharmacological assessment to identify potential safety liabilities in early drug discovery. Br J Pharmacol 154:1400–1413CrossRefGoogle Scholar
  62. 62.
    Oberdörster G, Oberdörster E, Oberdörster J (2005) Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 113:823–839CrossRefGoogle Scholar
  63. 63.
    Federici G, Shaw BJ, Handy RD (2007) Toxicity of titanium dioxide nanoparticles to rainbow trout (Oncorhynchus mykiss): Gill injury, oxidative stress, and other physiological effects. Aquat Toxicol 84:415–430CrossRefGoogle Scholar
  64. 64.
    Johnson AC, Bowes MJ, Crossley A, Jarvie HP, Jurkschat K, Jurgens MD, Lawlor AJ, Park B, Rowland P, Spurgeon D, Svendsen C, Thompson IP, Barnes RJ, Williams RJ, Xu N (2011) An assessment of the fate, behaviour and environmental risk associated with sunscreen TiO(2) nanoparticles in UK field scenarios. Sci Total Environ 409:2503–2510CrossRefGoogle Scholar
  65. 65.
    Perez S, Farre M, Barcelo D (2009) Analysis, behavior and ecotoxicity of carbon-based nanomaterials in the aquatic environment. Trends Analyt Chem 28:820–832CrossRefGoogle Scholar
  66. 66.
    Hao LH, Wang ZY, Xing BS (2009) Effect of sub-acute exposure to TiO(2) nanoparticles on oxidative stress and histopathological changes in Juvenile Carp (Cyprinus carpio). J Environ Sci (China) 21:1459–1466CrossRefGoogle Scholar
  67. 67.
    Zhu XS, Zhu L, Duan ZH, Qi RQ, Li Y, Lang YP (2008) Comparative toxicity of several metal oxide nanoparticle aqueous suspensions to zebrafish (Danio rerio) early developmental stage. J Environ Sci Health A Tox Hazard Subst Environ Eng 43:278–284CrossRefGoogle Scholar
  68. 68.
    Ramsden CS, Smith TJ, Shaw BJ, Handy RD (2009) Dietary exposure to titanium dioxide nanoparticles in rainbow trout, (Oncorhynchus mykiss): no effect on growth, but subtle biochemical disturbances in the brain. Ecotoxicology 18:939–951CrossRefGoogle Scholar
  69. 69.
    Hu YL, Gao JQ (2010) Potential neurotoxicity of nanoparticles. Int J Pharm 394:115–121CrossRefGoogle Scholar
  70. 70.
    Long TC, Saleh N, Tilton RD, Lowry GV, Veronesi B (2006) Titanium dioxide (P25) produces reactive oxygen species in immortalized brain microglia (BV2): implications for nanoparticle neurotoxicity. Environ Sci Technol 40:4346–4352CrossRefGoogle Scholar
  71. 71.
    Long TC, Tajuba J, Sama P, Saleh N, Swartz C, Parker J, Hester S, Lowry GV, Veronesi B (2007) Nanosize titanium dioxide stimulates reactive oxygen species in brain microglia and damages neurons in vitro. Environ Health Perspect 115:1631–1637CrossRefGoogle Scholar
  72. 72.
    Handy RD, Henry TB, Scown TM, Johnston BD, Tyler CR (2008) Manufactured nanoparticles: their uptake and effects on fish-a mechanistic analysis. Ecotoxicology 17:396–409CrossRefGoogle Scholar
  73. 73.
    Chen TH, Lin CY, Tseng MC (2011) Behavioral effects of titanium dioxide nanoparticles on larval zebrafish (Danio rerio). Mar Pollut Bull 63:303–308CrossRefGoogle Scholar
  74. 74.
    Xiong DW, Fang T, Yu LP, Sima XF, Zhu WT (2011) Effects of nano-scale TiO(2), ZnO and their bulk counterparts on zebrafish: acute toxicity, oxidative stress and oxidative damage. Sci Total Environ 409:1444–1452CrossRefGoogle Scholar
  75. 75.
    Jovanovic B, Ji TM, Palic D (2011) Gene expression of zebrafish embryos exposed to titanium dioxide nanoparticles and hydroxylated fullerenes. Ecotoxicol Environ Saf 74:1518–1525CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2011 2011

Authors and Affiliations

  • Demetrio Raldúa
    • 1
  • Carlos Barata
    • 1
  • Marta Casado
    • 1
  • Melissa Faria
    • 1
  • José María Navas
    • 2
  • Alba Olivares
    • 1
  • Eva Oliveira
    • 1
  • Sergi Pelayo
    • 1
  • Benedicte Thienpont
    • 1
  • Benjamin Piña
    • 1
    Email author
  1. 1.Institute of Environmental Assessment and Water Research (IDÆA-CSIC)BarcelonaSpain
  2. 2.Department of EnvironmentInstituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA)MadridSpain

Personalised recommendations