DOI QR코드

DOI QR Code

Norflurazon causes developmental defects including cardiovascular abnormalities in early-stage zebrafish (Danio rerio)

  • An, Garam (Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University) ;
  • Park, Hahyun (Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University) ;
  • Hong, Taeyeon (Department of Biological Sciences, Sungkyunkwan University) ;
  • Song, Gwonhwa (Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University) ;
  • Lim, Whasun (Department of Biological Sciences, Sungkyunkwan University)
  • Received : 2022.07.18
  • Accepted : 2022.08.30
  • Published : 2022.09.30

Abstract

Norflurazon is widely used on agricultural lands and has a high potential to pollute water sources. However, its effects on fish have not been fully elucidated. The purpose of our study was to determine whether norflurazon adversely affects the developmental stage of zebrafish, which are frequently used as a model system to evaluate the environmental impact of pollutants. Norflurazon interfered with the hatching of zebrafish embryos and induced several sublethal deformities including body length reduction, increased yolk sac volume, and enlargement of the pericardial region. We further examined the cardiotoxicity of norflurazon in the flk1:eGFP transgenic zebrafish line. The vascular network, mainly in the brain region, was significantly disrupted in norflurazon-exposed zebrafish. In addition, due to the failure of cardiac looping, norflurazon-exposed zebrafish had an abnormal cardiac structure. These developmental abnormalities were related to the apoptotic process triggered by norflurazon. Overall, the present study demonstrated the non-target toxicity of norflurazon by analyzing the hazardous effects of norflurazon on developing zebrafish.

Keywords

Acknowledgement

This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) grant funded by the Ministry of Education (2020R1A6A3A13075810 and 2019R1A6A1A10073079) and National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (2021R1A2C2005841). This study was also supported by the Institute of Animal Molecular Biotechnology, Korea University.

References

  1. An G, Park H, Song G, Lim W. 2021. Developmental toxicity of dimethachlor during zebrafish embryogenesis mediated by apoptosis and oxidative stress. J. Anim. Reprod. Biotechnol. 36:2-8. https://doi.org/10.12750/JARB.36.1.2
  2. Birke A and Scholz S. 2019. Zebrafish embryo and acute fish toxicity test show similar sensitivity for narcotic compounds. ALTEX 36:131-135. https://doi.org/10.14573/altex.1808101
  3. Busquet F, Strecker R, Rawlings JM, Belanger SE, Braunbeck T, Carr GJ, Cenijn P, Fochtman P, Gourmelon A, Hubler N, Kleensang A, Knobel M, Kussatz C, Legler J, Lillicrap A, Martinez-Jeronimo F, Polleichtner C, Rzodeczko H, Salinas E, Schneider KE, Scholz S, van den Brandhof EJ, van der Ven LT, Walter-Rohde S, Weigt S, Witters H, Halder M. 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. 69:496-511. https://doi.org/10.1016/j.yrtph.2014.05.018
  4. Chen J. 2013. Impaired cardiovascular function caused by different stressors elicits a common pathological and transcriptional response in zebrafish embryos. Zebrafish 10:389-400. (Erratum published 2014, Zebrafish 11:498)
  5. D'Costa A and Shepherd IT. 2009. Zebrafish development and genetics: introducing undergraduates to developmental biology and genetics in a large introductory laboratory class. Zebrafish 6:169-177. https://doi.org/10.1089/zeb.2008.0562
  6. Desgrange A, Le Garrec JF, Meilhac SM. 2018. Left-right asymmetry in heart development and disease: forming the right loop. Development 145:dev162776. https://doi.org/10.1242/dev.162776
  7. Fujita M, Cha YR, Pham VN, Sakurai A, Roman BL, Gutkind JS, Weinstein BM. 2011. Assembly and patterning of the vascular network of the vertebrate hindbrain. Development 138:1705-1715. https://doi.org/10.1242/dev.058776
  8. Glaberman S, Padilla S, Barron MG. 2017. Evaluating the zebrafish embryo toxicity test for pesticide hazard screening. Environ. Toxicol. Chem. 36:1221-1226. https://doi.org/10.1002/etc.3641
  9. Gupta A, Rarick KR, Ramchandran R. 2021. Established, new and emerging concepts in brain vascular development. Front. Physiol. 12:636736. https://doi.org/10.3389/fphys.2021.636736
  10. Ha Y, Kim Y, Choi J, Hwang I, Ko JY, Jeon HK, Kim YJ. 2021. Evaluation of cytotoxicity, genotoxicity, and zebrafish embryo toxicity of mixtures containing Hyssopus officinalis, Morus alba, Engraulis japonicus, and 27 other extracts for cosmetic safety assessment. Mol. Cell. Toxicol. 17:221-232. https://doi.org/10.1007/s13273-021-00128-7
  11. Hill AJ, Teraoka H, Heideman W, Peterson RE. 2005. Zebrafish as a model vertebrate for investigating chemical toxicity. Toxicol. Sci. 86:6-19. https://doi.org/10.1093/toxsci/kfi110
  12. Horvat T, Kalafatic M, Kopjar N, Kovacevic G. 2005. Toxicity testing of herbicide norflurazon on an aquatic bioindicator species--the planarian Polycelis felina (Daly.). Aquat. Toxicol. 73:342-352. https://doi.org/10.1016/j.aquatox.2005.03.023
  13. Horzmann KA, Portales AM, Batcho KG, Freeman JL. 2020. Developmental toxicity of trichloroethylene in zebrafish (Danio rerio). Environ. Sci. Process. Impacts 22:728-739. https://doi.org/10.1039/C9EM00565J
  14. Huang S, Huang M, Tian S, Meng Z, Yan S, Teng M, Zhou Z, Diao J, Zhu W. 2022. Imazalil and its metabolite imazalil-M caused developmental toxicity in zebrafish (Danio rerio) embryos via cell apoptosis mediated by metabolic disorders. Pestic. Biochem. Physiol. 184:105113. https://doi.org/10.1016/j.pestbp.2022.105113
  15. Kucukoglu M, Binokay US, Pekmezekmek AB. 2013. The effects of zinc chloride during early embryonic development in zebrafish (Brachydanio rerio). Turk. J. Biol. 37:158-164.
  16. Munn MD and Gilliom RJ. 2001. Pesticide Toxicity Index for Freshwater Aquatic Organisms. U.S. Department of the Interior, U.S. Geological Survey, Sacramento, pp. 34.
  17. Park H, Song G, Lim W. 2021. Isoprocarb induces acute toxicity in developing zebrafish embryos through vascular malformation. J. Anim. Reprod. Biotechnol. 36:17-24. https://doi.org/10.12750/JARB.36.1.17
  18. Parlak V. 2018. Evaluation of apoptosis, oxidative stress responses, AChE activity and body malformations in zebrafish (Danio rerio) embryos exposed to deltamethrin. Chemosphere 207:397-403. https://doi.org/10.1016/j.chemosphere.2018.05.112
  19. Sant KE and Timme-Laragy AR. 2018. Zebrafish as a model for toxicological perturbation of yolk and nutrition in the early embryo. Curr. Environ. Health Rep. 5:125-133. https://doi.org/10.1007/s40572-018-0183-2
  20. Sathishkumar P, Mangalaraja RV, Rozas O, Vergara C, Mansilla HD, Gracia-Pinilla MA, Anandan S. 2016. Sonophotocatalytic mineralization of Norflurazon in aqueous environment. Chemosphere 146:216-225. https://doi.org/10.1016/j.chemosphere.2015.12.011
  21. Schuler LJ and Rand GM. 2008. Aquatic risk assessment of herbicides in freshwater ecosystems of South Florida. Arch. Environ. Contam. Toxicol. 54:571-583. https://doi.org/10.1007/s00244-007-9085-2
  22. Smirnova A, Mentor A, Ranefall P, Bornehag CG, Brunstrom B, Mattsson A, Jonsson M. 2021. Increased apoptosis, reduced Wnt/β-catenin signaling, and altered tail development in zebrafish embryos exposed to a human-relevant chemical mixture. Chemosphere 264(Pt 1):128467. https://doi.org/10.1016/j.chemosphere.2020.128467
  23. Tessadori F, Tsingos E, Colizzi ES, Kruse F, van den Brink SC, van den Boogaard M, Christoffels VM, Merks RM, Bakkers J. 2021. Twisting of the zebrafish heart tube during cardiac looping is a tbx5-dependent and tissue-intrinsic process. Elife 10:e61733. https://doi.org/10.7554/eLife.61733
  24. Wang Q, Liu S, Hu D, Wang Z, Wang L, Wu T, Wu Z, Mohan C, Peng A. 2016. Identification of apoptosis and macrophage migration events in paraquat-induced oxidative stress using a zebrafish model. Life Sci. 157:116-124. https://doi.org/10.1016/j.lfs.2016.06.009
  25. Wilson PC, Boman B, Foos JF. 2007. Norflurazon and simazine losses in surface runoff water from flatwoods citrus production areas. Bull. Environ. Contam. Toxicol. 78:341-344. https://doi.org/10.1007/s00128-007-9202-y
  26. Wilson PC and Koch R. 2013. Influence of exposure concentration and duration on effects and recovery of Lemna minor exposed to the herbicide norflurazon. Arch. Environ. Contam. Toxicol. 64:228-234. https://doi.org/10.1007/s00244-012-9834-8
  27. Zoupa M and Machera K. 2017. Zebrafish as an alternative vertebrate model for investigating developmental toxicity-the triadimefon example. Int. J. Mol. Sci. 18:817. https://doi.org/10.3390/ijms18040817