Toxicological, gene expression and histopathological evaluations of environmentally realistic concentrations of polybrominated diphenyl ethers PBDE- 47, PBDE-99 and PBDE-209 on zebrafish embryos (original) (raw)

Abstract

Polybrominated diphenyl ethers (PBDEs) are brominated flame retardants. Biomonitoring studies have shown widespread presence of PBDEs in humans and their accumulation in food chain cause concern to human health, especially for foetus and infant development. The early-life stages are generally considered more sensitive to exposure to toxic compounds than juvenile or adults. For this reason the aim of this study was to evaluate the effects of the three most environmentally relevant BDE (BDE-47, 99 and 209) on zebrafish embryos. The fish embryo toxicity (FET) OECD tests on zebrafish were performed followed by histopathogical examination to assess morphological changes. The gene expression of the thyroid stimulating hormone β (Tshβ), the transport proteins transthyretin (Ttr) and thyroxine-binding globulin (Tbg) as well as the enzyme iodothyronine deiodinase 1 (Dio1) was also assessed by Real-time PCR. BDE-47 and BDE-99 showed an increase of the severity of the effects at the lower concentrations while for the BDE-209 the effects were higher to the high concentrations. Although all compounds did not show any acute toxicity for none of the concentrations tested, they reported interesting sub-acute lesions, including yolk and pericardial edema, tail and head malformation, reduced and extremely reduced heart beat rate, blood stasis and spinal curvature, with the highest percentage recorded for BDE-209. Cardiac edema, damage of eye structure and hydrocephaly were confirmed also by histophatological examination. Furthermore, a toxic and dose-dependent liver vacuolization in BDE-209 was observed in all experimental groups. Although no statistically significant difference in gene expression was observed, BDE-209 up-regulated only Dio1 while the other congeners induced Tshβ, Ttr, Tbg and Dio1. Overall, this research highlighted that exposure to BDE-47, BDE-99 and BDE-209 at realistic concentrations caused lethal and sub-lethal alterations and impaired genes involved in thyroid hormones homeostasis leading to abnormal development of zebrafish embryos.

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References (42)

  1. Bruchajzer, E., Frydrych, B., Sporny, S., Szymańska, J.A., 2010. Toxicity of penta-and decabromodiphenyl ethers after repeated administration to rats: a comparative study. Arch. Toxicol. 84 (4), 287-299.
  2. Bruchajzer, E., Frydrych, B., Sporny, S., Szymańska, J.A., 2011. The effect of short-term intoxication of rats with pentabromodiphenyl ether (in mixture mimic commercial products). Hum. Exp. Toxicol. 30 (5), 363-378.
  3. Chan, W.K., Chan, K.M., 2012. Disruption of the hypothalamic-pituitary-thyroid axis in zebrafish embryo-larvae following waterborne exposure to BDE-47, TBBPA and BPA. Aquat. Toxicol. 108, 106-111.
  4. Chen, L., Zhu, B., Guo, Y., Xu, T., Lee, J.S., Qian, P.Y., Zhou, B., 2016. High-throughput transcriptome sequencing reveals the combined effects of key e-waste contaminants, decabromodiphenyl ether (BDE-209) and lead, in zebrafish larvae. Environ. Pollut. 214, 324-333.
  5. Chen, Q., Yu, L., Yang, L., Zhou, B., 2012. Bioconcentration and metabolism of deca- bromodiphenyl ether (BDE-209) result in thyroid endocrine disruption in zebrafish larvae. Aquat. Toxicol. 110, 141-148.
  6. Costa, L.G., Giordano, G., 2007. Developmental neurotoxicity of polybrominated di- phenyl ether (PBDE) flame retardants. Neurotoxicology (Little Rock) 28 (6), 1047-1067.
  7. Covaci, A., Harrad, S., Abdallah, M.A.E., Ali, N., Law, R.J., Herzke, D., de Wit, C.A., 2011. Novel brominated flame retardants: a review of their analysis, environmental fate and behaviour. Environ. Int. 37 (2), 532-556.
  8. EFSA, 2011. Scientific opinion on polybrominated diphenyl ethers (PBDEs) in food. EFSA Journal 9 (5), 2156.
  9. Ellis, J.L., Yin, C., 2017. Histological analyses of acute alcoholic liver injury in zebrafish. J. Vis. Exp. JoVE(123).
  10. Foekema, E.M., Deerenberg, C.M., Murk, A.J., 2008. Prolonged ELS test with the marine flatfish sole (Solea solea) shows delayed toxic effects of previous exposure to PCB 126. Aquat. Toxicol. 90 (3), 197-203.
  11. Giraudo, M., Douville, M., Letcher, R.J., Houde, M., 2017. Effects of food-borne exposure of juvenile rainbow trout (Oncorhynchus mykiss) to emerging brominated flame re- tardants 1, 2-bis (2, 4, 6-tribromophenoxy) ethane and 2-ethylhexyl-2, 3, 4, 5-tet- rabromobenzoate. Aquat. Toxicol. 186, 40-49.
  12. Han, Z., Li, Y., Zhang, S., Song, N., Xu, H., Dang, Y., Yu, H., 2017. Prenatal transfer of decabromodiphenyl ether (BDE-209) results in disruption of the thyroid system and developmental toxicity in zebrafish offspring. Aquat. Toxicol. 190, 46-52.
  13. Ji, C., Wu, H., Wei, L., Zhao, J., Lu, H., Yu, J., 2013a. Proteomic and metabolomic analysis of earthworm Eisenia fetida exposed to different concentrations of 2, 2′, 4, 4′-tetra- bromodiphenyl ether. J. Proteomics 91, 405-416.
  14. Ji, C., Wu, H., Wei, L., Zhao, J., Yu, J., 2013b. Proteomic and metabolomic analysis reveal gender-specific responses of mussel Mytilus galloprovincialis to 2, 20, 4, 40-tetra- bromodiphenyl ether (BDE 47). Aquat. Toxicol. 140, 449e457.
  15. Katima, Z., Okonkwo, J.O., Daso, A.P., 2017. A review of brominated flame retardants in the environment with emphasis on atmospheric levels, knowledge and information gaps in the African continent. Atmos. Pollut. Res. 8 (4), 767-780.
  16. Law, R.J., Covaci, A., Harrad, S., Herzke, D., Abdallah, M.A.E., Fernie, K., Takigami, H., 2014. Levels and trends of PBDEs and HBCDs in the global environment: status at the end of 2012. Environ. Int. 65, 147-158.
  17. Linares, V., Bellés, M., Domingo, J.L., 2015. Human exposure to PBDE and critical eva- luation of health hazards. Arch. Toxicol. 89 (3), 335-356.
  18. Macaulay, L.J., Chernick, M., Chen, A., Hinton, D.E., Bailey, J.M., Kullman, S.W., Stapleton, H.M., 2017. Exposure to a PBDE/OH-BDE mixture alters juvenile zebrafish (Danio rerio) development. Environ. Toxicol. Chem. 36 (1), 36-48.
  19. Meerts, I.A., Van Zanden, J.J., Luijks, E.A., van Leeuwen-Bol, I., Marsh, G., Jakobsson, E., Brouwer, A., 2000. Potent competitive interactions of some brominated flame re- tardants and related compounds with human transthyretin in vitro. Toxicol. Sci. 56 (1), 95-104 Mitochondrial permeability transition and impairs mitochondrial bioe- nergetics. J. Toxicol. Environ. Health A 77(1-3), 24-36.
  20. Nagel, R., 2002. DarT: the embryo test with the zebrafish Danio rerio-a general model in ecotoxicology and toxicology. ALTEX 19 (Suppl. 1), 38-48.
  21. OECD, 1992. Test No. 203: Fish, Acute Toxicity Test. OECD, Guideline for Testing of Chemicals. OECD pub.
  22. OECD, 2013. Test No. 236: Fish Embryo Acute Toxicity (FET) Test. OECD, Guideline for Testing of Chemicals. OECD pub.
  23. Pereira, L.C., Miranda, L.F.C., de Souza, A.O., Dorta, D.J., 2014. BDE-154 induces. Pietroń, W.J., Małagocki, P., 2017. Quantification of polybrominated diphenyl ethers (PBDEs) in food. A review. Talanta 167, 411-427.
  24. Primer designing tool -NCBI -NIH, www.ncbi.nlm.nih.gov/tools/primer-blast..
  25. Souza, A.O., Pereira, L.C., Oliveira, D.P., Dorta, D.J., 2013. BDE-99 congener induces cell death by apoptosis of human hepatoblastoma cell line-HepG2. Toxicol. In Vitro 27 (2), 580-587.
  26. Stapleton, H.M., Sharma, S., Getzinger, G., Ferguson, P.L., Gabriel, M., Webster, T.F., Blum, A., 2012. Novel and high volume use flame retardants in US couches reflective of the 2005 PentaBDE phase out. Environ. Sci. Technol. 46 13432e13439.
  27. Tait, S., Perugini, M., La Rocca, C., 2017. Relative toxicological ranking of eight poly- brominated diphenyl ether congeners using cytotoxicity, chemical properties and exposure data. Food Chem. Toxicol. 108, 74-84.
  28. UNEP, 2013. Proposal to list decabromodiphenyl ether (commercial Mixture, c-decaBDE) in annex A, B and/or C to the Stockholm Convention on persistent organic pollutants. UNEP/POPS/POPRC.9/2.
  29. Van der Geyten, S., Byamungu, N., Reyns, G.E., Kühn, E.R., Darras, V.M., 2005. Iodothyronine deiodinases and the control of plasma and tissue thyroid hormone levels in hyperthyroid tilapia (Oreochromis niloticus). J. Endocrinol. 184 (3), 467-479.
  30. Verner, M.A., Bouchard, M., Fritsche, E., Charbonneau, M., Haddad, S., 2011. In vitro neurotoxicity data in human risk assessment of polybrominated diphenyl ethers (PBDEs): overview and perspectives. Toxicol. In Vitro 25 (8), 1509-1515.
  31. Wu, M., Wu, D., Wang, C., Guo, Z., Li, B., Zuo, Z., 2016. Hexabromocyclododecane ex- posure induces cardiac hypertrophy and arrhythmia by inhibiting miR-1 expression via up-regulation of the homeobox gene Nkx2. 5. J. Hazard Mater. 302, 304-313.
  32. Xu, T., Zhao, J., Yin, D., Zhao, Q., Dong, B., 2015. High-throughput RNA sequencing reveals the effects of 2,2′,4,4′ -tetrabromodiphenyl ether on retina and bone devel- opment of zebrafish larvae. BMC Genomics 16, 23.
  33. Yang, J., Chan, K.M., 2015. Evaluation of the toxic effects of brominated compounds (BDE-47, 99, 209, TBBPA) and bisphenol A (BPA) using a zebrafish liver cell line. ZFL. Aquat. Toxicol. 159, 138-147.
  34. Yang, J., Zhao, H., Chan, K.M., 2017. Toxic effects of polybrominated diphenyl ethers (BDE 47 and 99) and localization of BDE-99-induced cyp1a mRNA in zebrafish larvae. Toxicol. Rep. 4, 614-624.
  35. Yu, L., Chen, M., Liu, Y., Gui, W., Zhu, G., 2013. Thyroid endocrine disruption in zebrafish larvae following exposure to hexaconazole and tebuconazole. Aquat. Toxicol. 138, 35-42.
  36. Zhai, W., Huang, Z., Chen, L., Feng, C., Li, B., Li, T., 2014. Thyroid endocrine disruption in zebrafish larvae after exposure to mono-(2-ethylhexyl) phthalate (MEHP). PLoS One 9 (3), e92465.
  37. Zhang, Z.F., Shan, Q., Zhuang, J., Zhang, Y.Q., Wang, X., Fan, S.H., Zheng, Y.L., 2015b. Troxerutin inhibits 2, 2′, 4, 4′-tetrabromodiphenyl ether (BDE-47)-induced hepato- cyte apoptosis by restoring proteasome function. Toxicol. Lett. 233 (3), 246-257.
  38. Zhang, Z.F., Zhang, Y.Q., Fan, S.H., Zhuang, J., Zheng, Y.L., Lu, J., Hu, B., 2015a. Troxerutin protects against 2, 2′, 4, 4′-tetrabromodiphenyl ether (BDE-47)-induced liver inflammation by attenuating oxidative stress-mediated NAD+-depletion. J. Hazard Mater. 283, 98-109.
  39. Zhao, X., Ren, X., Ren, B., Luo, Z., Zhu, R., 2016. Life-cycle exposure to BDE-47 results in thyroid endocrine disruption to adults and offsprings of zebrafish (Danio rerio). Environ. Toxicol. Pharmacol. 48, 157-167.
  40. Zhou, S.N., Buchar, A., Siddique, S., Takser, L., Abdelouahab, N., Zhu, J., 2014. Measurements of selected brominated flame retardants in nursing women: implica- tions for human exposure. Environ. Sci. Technol. 48 (15), 8873-8880.
  41. Zoeller, R.T., Rovet, J., 2004. Timing of thyroid hormone action in the developing brain: clinical observations and experimental findings. J. Neuroendocrinol. 16 (10), 809-881.
  42. D. Zezza, et al. Ecotoxicology and Environmental Safety 183 (2019) 109566