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Zebrafish as a model system for biomedical studies

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Abstract

Zebrafish (Danio rerio) is now firmly recognized as a powerful research model for many areas of biology and medicine. Here, we review some achievements of zebrafish-based assays for modeling human diseases and for drug discovery and development. For drug discovery, zebrafish is especially valuable during the earlier stages of research as its represents a model organism to demonstrate a new treatment’s efficacy and toxicity before more costly mammalian models are used. This review considers some examples of known compounds which exhibit both physiological activity and toxicity in humans and zebrafish. The major advantages of zebrafish embryos consist in their permeability to small molecules added to their incubation medium and chorion transparency that enables the easy observation of the development. Assay of acute toxicity (LC50 estimation) in embryos can also include the screening for developmental disorders as an indicator of teratogenic effects. We have used the zebrafish model for toxicity testing of new drugs based on phospholipid nanoparticles (e.g. doxorubicin). Genome organization and the pathways involved into control of signal transduction appear to be highly conserved between zebrafish and humans and therefore zebrafish may be used for modeling of human diseases. The review provides some examples of zebrafish application in this field.

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References

  1. Rubinstein, A.L., Expert Opin. Drug Metabol. Toxicol., 2006, vol. 2, pp. 231–240.

    Article  CAS  Google Scholar 

  2. Kari, G., Rodeck, U., and Dicker, A.P., Clin. Pharmacol. Therapet., 2007, vol. 82, pp. 70–80.

    Article  CAS  Google Scholar 

  3. Lieschke, G.J. and Currie, P.D., Nature Reviews Genetics, 2007, vol. 8, pp. 353–367.

    Article  CAS  Google Scholar 

  4. Crawford, A.D., Esguerra, C.V., and de Witte, P.A.M., Planta Med., 2008, vol. 74, pp. 624–632.

    Article  CAS  Google Scholar 

  5. Berghmans, S., Butler, P., Goldsmith, P., Waldron, G., Gardner, I., Golder, Z., Richards, F.M., Kimber, G., Roach, A., Alderton, W., and Fleming, A., J. Pharmacol. Toxicol. Methods, 2008, vol. 58, pp. 59–68.

    Article  CAS  Google Scholar 

  6. McGrath, P. and Li, Chun-Q., Drug Discov. Today, 2008, vol. 13, pp. 394–401.

    Article  CAS  Google Scholar 

  7. Langheinrich, U., Bioassays, 2003, vol. 25, pp. 904–912.

    Article  CAS  Google Scholar 

  8. ISO 7346-1:1996.

  9. OECD (1992) Test Guideline 203. OECD Guideline for Testing of Chemicals. Fish, Acute Toxicity Test.

  10. Vosylien, Z., Acta Zoolog. Lituanica, 2007, vol. 17, pp. 3–15.

    Google Scholar 

  11. Braunbeck, T., Böttcher, M., Holler, H., Kosmeh, T., Lammer, E., Leist, E., Rudolf, M., and Seitz, N., ALTEX, 2005, vol. 22, pp. 87–102.

    Google Scholar 

  12. Nagel, R., ALTEX, 2002, vol. 19, pp. 38–48.

    Google Scholar 

  13. Braunbeck, T. and Lammer, E., Background Paper on Fish Embryo Toxicity Assays (UBA Contract Number 20385422) German Federal Environmental Agency, Dessau, 2006.

    Google Scholar 

  14. OECD, Guideline for Testing of Chemicals. Draft Proposal for a New Guideline. Fish Embryo Toxicity (FET) Test, 2006.

  15. Scholz, S., Fischer, S., Gündel, U., Küster, E., Luckenbach, T., and Voelker, D., Environ. Sci. Pollut. Res., 2008, vol. 15, pp. 394–404.

    Article  CAS  Google Scholar 

  16. Parng, C., Wen Lin, Seng, Semino, C., and McGrath, P., Assay and Drug Develop. Technol., 2002, vol. 1, pp. 1–8.

    Article  Google Scholar 

  17. Tanguay, R.L., Neurotoxicol. Teratol., 2006, vol. 28, pp. 497–508.

    Article  Google Scholar 

  18. Arenzana, F.J., Carvan, M.J., Aijón, J., Sánchez-González, R., Arévalo, R., and Porteros, A., Neurotoxicol. Teratol., 2006, vol. 28, pp. 342–348.

    Article  CAS  Google Scholar 

  19. Carvan, M.J., Loucksa, E., Weberb, D.N., and Williams, F.E., Neurotoxicol. Teratol., 2004, vol. 26, pp. 757–768.

    Article  CAS  Google Scholar 

  20. Seng, W.L., Toxicologist, 2007, vol. 96(Suppl.), p. 145.

    Google Scholar 

  21. Zon, L. and Peterson, R.T., Nature. Rev. Drug Discov., 2005, vol. 4, pp. 35–44.

    Article  CAS  Google Scholar 

  22. Folkman, J., Nature Rev. Drug Discov., 2007, vol. 6, pp. 273–286.

    Article  CAS  Google Scholar 

  23. Serbedzija, G. N., Angiogenesis, 1999, vol. 3, pp. 353–359.

    Article  CAS  Google Scholar 

  24. Kidd, K.R. and Weinstein, B.M., British J. Pharmacol., 2003, vol. 140, pp. 585–594.

    Article  CAS  Google Scholar 

  25. Cross, L.M., Cook, M.A., Lin, S., Chen, J.N., and Rubinstein, A.L., Arterioscler. Thromb. Vasc. Biol., 2003, vol. 23, pp. 911–912.

    Article  CAS  Google Scholar 

  26. Langheinrich, U., Hennen, E., Stot, G., and Vacun, G., Curr. Biol., 2002, vol. 12, pp. 2023–2028.

    Article  CAS  Google Scholar 

  27. Ton, C. and Parng, C., Hear. Res., 2005, vol. 208, pp. 79–88.

    Article  CAS  Google Scholar 

  28. Zhang, C., Willett, C., and Fremgen, T., Curr. Protoc. Toxicol., 2003, pp. 1.7.1–1.7.18.

  29. Chaoyong, M.A., Amer. Chem. Soc. Modern Drug Discovery, 2004, pp. 30–36.

  30. Goldsmith, P., Curr. Opinion in Pharmacol., 2004, vol. 4, pp. 504–512.

    Article  CAS  Google Scholar 

  31. Mlan, D.J., Peterson, T.A., Ruskin, J.N., Peterson, R.T., and MacRae, C.A., Circulation, 2003, vol. 107, pp. 1355–1358.

    Article  Google Scholar 

  32. Boehmler, W., Carr, T., Thisse, C., Thisse, B., Canfield, V.A., and Levenson, R., Genes Brain Behav., 2007, vol. 6, pp. 155–166.

    Article  CAS  Google Scholar 

  33. Airhart, M.J., Lee, D.H., Wilson, T.D., Miller, B.E., Miller, M.N., and Skalko, R.G., Neurotoxicol. Teratol., 2007, vol. 29, pp. 652–664.

    Article  CAS  Google Scholar 

  34. Zhdanova, I.V., Wang, S.Y., Leclair, O.U., and Danilova, N.P., Brain Res., 2001, vol. 903, pp. 263–268.

    Article  CAS  Google Scholar 

  35. Lockwood, B., Bjerke, S., Kobayashi, K., and Guo, S., Pharmacol. Biochem. Behav., 2004, vol. 77, pp. 647–654.

    Article  CAS  Google Scholar 

  36. Barros, T.P., Alderton W.K., Reynolds, H.M., Roach, A.G., and Berghmans, S., British J. Pharmacol., 2008, vol. 154, pp. 1400–1413.

    Article  CAS  Google Scholar 

  37. Heiden, T.C, Dengler, E., Kao, W.J., Heideman, W., and Peterson, R.E., Toxicol. Appl. Pharmacol., 2007, vol. 225, pp. 70–79.

    Article  Google Scholar 

  38. Lee, K.J., Nallathamby, P.D., Browning, L.M., Osgood, C.J., and Xu, X.N., ACSNANO, 2007, vol. 1, pp. 133–144.

    CAS  Google Scholar 

  39. Gundel, U., Benndorf, D., von Bergen, M., Altenburger, R., and Kuster, E., Proteomics, 2007, vol. 7, pp. 4541–4554.

    Article  Google Scholar 

  40. Tseng, H.P., Hseu, T.H., Buhler, D.R., Wang, W.D., and Hu, C.H., Toxicol. Appl. Pharmacol., 2005, vol. 205, pp. 247–258.

    Article  CAS  Google Scholar 

  41. Li, C.Q., Toxicologist, 2008, vol. 97(Suppl.), p. 148.

    Google Scholar 

  42. Dean, M. and Annilo, T., Annu. Rev. Genomics Hum. Genet., 2005, vol. 6, pp. 123–142.

    Article  CAS  Google Scholar 

  43. Lam, C.S., Korz, H.V., and Strahl, E.U., Eur. J. Neurosci., 2005, vol. 21, pp. 1758–1762.

    Article  Google Scholar 

  44. Gerhard, G.S., Experimen. Gerontol., 2003, vol. 38, pp. 1333–1341.

    Article  CAS  Google Scholar 

  45. Elo, B., Villano, C.M., Govorco, D., and White, L.A., J. Mol. Endocinol., 2007, vol. 38, pp. 433–440.

    Article  CAS  Google Scholar 

  46. Pyati, U.J., Look, A.T., and Hammerschmidt, M., Semin. Cancer Biol., 2007, vol. 17, pp. 154–165.

    Article  CAS  Google Scholar 

  47. Silva, M.T., Vale, A., and dos Santos, N.M.S., Curr. Pharmac. Design, 2008, vol. 14, pp. 170–183.

    Article  CAS  Google Scholar 

  48. Meng, X.W., Lee, S.H., and Kaufmann, S.H., Curr. Opin. Cell Biol., 2006, vol. 18, pp. 668–676.

    Article  CAS  Google Scholar 

  49. dos Santos, N.M.S., do Vale, A., Reis, M.I.R., and Silva, M.T., Curr. Pharmaceut. Design, 2008, vol. 14, pp. 148–169.

    Article  Google Scholar 

  50. Rubinstein, A.L., Curr. Opinion in Drug Discov. Develop., 2003, vol. 6, pp. 218–223.

    CAS  Google Scholar 

  51. Spitsbergen, J.M. and Kent, M.L., Toxicol. Pathol., 2003, vol. 31(Suppl), pp. 62–87.

    CAS  Google Scholar 

  52. Mizgireuv, I.V. and Revskoy, S.Y., Cancer Res., 2006, vol. 66, pp. 3120–3125.

    Article  CAS  Google Scholar 

  53. Patton, E.E., Widlund, H.R., Kutok, J.L., Kopani, K.R., Amatruda, J.F., Murphey, R.D., Berghmans, S., Mayhall, E.A., Traver, D., Fletcher, C.D., Aster, J.C., Granter, S.R., Look, A.T., Lee, C., Fisher, D.E., and Zon, L.I., Curr. Biol., 2005, vol. 15, pp. 249–254.

    Article  CAS  Google Scholar 

  54. Meeker, N.D. and Trede, N.S., Develop. Compar. Immunol., 2008, vol. 32, pp. 745–757.

    CAS  Google Scholar 

  55. http:/ /zfish.org.

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Correspondence to N. F. Belyaeva.

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Original Russian Text © N.F. Belyaeva, V.N. Kashirtseva, N.V. Medvedeva, Yu.Yu. Khudoklinova, O.M. Ipatova, A. I. Archakov, 2009, published in Biomeditsinskaya Khimiya.

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Belyaeva, N.F., Kashirtseva, V.N., Medvedeva, N.V. et al. Zebrafish as a model system for biomedical studies. Biochem. Moscow Suppl. Ser. B 3, 343–350 (2009). https://doi.org/10.1134/S1990750809040039

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  • DOI: https://doi.org/10.1134/S1990750809040039

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