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Protective Effects of Spermidine and Melatonin on Deltamethrin-Induced Cardiotoxicity and Neurotoxicity in Zebrafish

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Abstract

Increased application of the pyrethroid insecticide deltamethrin has adverse effects on the cardiac system and neurobehavior on the non-target organisms, which has raised the public’s attention. Because of spermidine and melatonin considered to have cardioprotective and neuroprotective characteristics, zebrafish were utilized as the model organism to explore the protective effects of spermidine and melatonin against deltamethrin-induced toxicity. We tested the neurobehavior of zebrafish larvae through a rest/wake behavior assay, and evaluated the levels of the expression of Scn5lab, gata4, nkx2.5, hcrt, hcrtr, and aanat2 by qRT-PCR. Besides that cmlc2 was evaluated by whole-mount in situ hybridization. Results have shown that compared with control group, 0.025 mg/L deltamethrin could significantly disturb the cardiac development, downregulating the expression of Scn5lab and transcriptional factors gata4 and nkx2.5, disturbing cardiac loo**, resulting in defects in cardiac morphology and function. Moreover, deltamethrin could alter the expression levels of rest/wake genes and cause hyperactivity in zebrafish larvae. Besides, compared with deltamethrin group, the exogenous 0.01 mg/L spermidine and 0.232 mg/L melatonin could significantly rescue the adverse effects of deltamethrin on the cardiac system and neurobehavior in zebrafish. This indicated that spermidine and melatonin have neuroprotective and cardioprotective effects against deltamethrin-induced adverse effects in zebrafish.

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References

  1. Elliott, M., Farnham, A. W., Janes, N. F., Needham, P. H., & Pulman, D. A. (1974). Synthetic insecticide with a new order of activity. Nature, 248, 710–711.

    Article  CAS  PubMed  Google Scholar 

  2. Soderlund, D. M. (2012). Molecular mechanisms of pyrethroid insecticide neurotoxicity: Recent advances. Archives of Toxicology, 86, 165–181.

    Article  CAS  PubMed  Google Scholar 

  3. Bouwman, H., Sereda, B., & Meinhardt, H. M. (2006). Simultaneous presence of DDT and pyrethroid residues in human breast milk from a malaria endemic area in South Africa. Environmental Pollution, 144, 902–917.

    Article  CAS  PubMed  Google Scholar 

  4. Whyatt, R. M., Garfinkel, R., Hoepner, L. A., Holmes, D., Borjas, M., Williams, M. K., et al. (2007). Within- and between-home variability in indoor-air insecticide levels during pregnancy among an inner-city cohort from New York City. Environmental Health Perspectives, 115, 383–389.

    Article  CAS  PubMed  Google Scholar 

  5. Naeher, L. P., Tulve, N. S., Egeghy, P. P., Barr, D. B., Adetona, O., Fortmann, R. C., et al. (2010). Organophosphorus and pyrethroid insecticide urinary metabolite concentrations in young children living in a southeastern United States city. Science of the Total Environment, 408, 1145–1153.

    Article  CAS  PubMed  Google Scholar 

  6. Richardson, J. R., Taylor, M. M., Shalat, S. L., Guillot, T. S., Caudle, W. M., Hossain, M. M., et al. (2015). Developmental pesticide exposure reproduces features of attention deficit hyperactivity disorder. The FASEB Journal, 29, 1960–1972.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Dhivya Vadhana, M. S., Siva Arumugam, S., Carloni, M., Nasuti, C., & Gabbianelli, R. (2013). Early life permethrin treatment leads to long-term cardiotoxicity. Chemosphere, 93, 1029–1034.

    Article  CAS  PubMed  Google Scholar 

  8. Luo, H., Masika, J., Guan, X., Nie, L., Ao, D., Qi, Y., et al. (2019). Long term perinatal deltamethrin exposure alters electrophysiological properties of embryonic ventricular cardiomyocyte. Current Medical Science, 39, 21–27.

    Article  CAS  PubMed  Google Scholar 

  9. Widmark, J., Sundstrom, G., Ocampo Daza, D., & Larhammar, D. (2011). Differential evolution of voltage-gated sodium channels in tetrapods and teleost fishes. Molecular Biology and Evolution, 28, 859–871.

    Article  CAS  PubMed  Google Scholar 

  10. Moreno, J. D., & Clancy, C. E. (2012). Pathophysiology of the cardiac late Na current and its potential as a drug target. Journal of Molecular and Cellular Cardiology, 52, 608–619.

    Article  CAS  PubMed  Google Scholar 

  11. Mahboob, S., Niazi, F., AlGhanim, K., Sultana, S., Al-Misned, F., & Ahmed, Z. (2015). Health risks associated with pesticide residues in water, sediments and the muscle tissues of Catla catla at Head Balloki on the River Ravi. Environmental Monitoring and Assessment, 187, 81.

    Article  PubMed  CAS  Google Scholar 

  12. Kylin, H. B. A. H. (2014). Malaria control insecticide residues in breast milk: The need to consider infant health risks. Environmental Health Perspectives, 117(10), 1477–1480.

    Google Scholar 

  13. Li, M., Liu, X., & Feng, X. (2019). Cardiovascular toxicity and anxiety-like behavior induced by deltamethrin in zebrafish (Danio rerio) larvae. Chemosphere, 219, 155–164.

    Article  CAS  PubMed  Google Scholar 

  14. Raina, A., & Jänne, J. (1975). Physiology of the natural polyamines putrescine, spermidine and spermine. Medicine and Biology, 53, 121–147.

    CAS  Google Scholar 

  15. Eisenberg, T., Knauer, H., Schauer, A., Büttner, S., Ruckenstuhl, C., Carmona-Gutierrez, D., et al. (2009). Induction of autophagy by spermidine promotes longevity. Nature Cell Biology, 11, 1305–1314.

    Article  CAS  PubMed  Google Scholar 

  16. Eisenberg, T., Abdellatif, M., Schroeder, S., Primessnig, U., Stekovic, S., Pendl, T., et al. (2016). Cardioprotection and lifespan extension by the natural polyamine spermidine. Nature Medicine, 22, 1428–1438.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Sharma, S., Kumar, P., & Deshmukh, R. (2018). Neuroprotective potential of spermidine against rotenone induced Parkinson's disease in rats. Neurochemistry International, 116, 104–111.

    Article  CAS  PubMed  Google Scholar 

  18. Karbownik, M., & Reiter, R. J. (2000). Antioxidative effects of melatonin in protection against cellular damage caused by ionizing radiation. Proceedings of the Society for Experimental Biology and Medicine, 225, 9–22.

    Article  CAS  PubMed  Google Scholar 

  19. Iggena, D., Winter, Y., & Steiner, B. (2017). Melatonin restores hippocampal neural precursor cell proliferation and prevents cognitive deficits induced by jet lag simulation in adult mice. Journal of Pineal Research, 62, e12397.

    Article  CAS  Google Scholar 

  20. Calvo, J. R., Gonzalez-Yanes, C., & Maldonado, M. D. (2013). The role of melatonin in the cells of the innate immunity: A review. Journal of Pineal Research, 55, 103–120.

    Article  CAS  PubMed  Google Scholar 

  21. Su, S.-C., Hsieh, M.-J., Yang, W.-E., Chung, W.-H., Reiter, R. J., & Yang, S.-F. (2017). Cancer metastasis: Mechanisms of inhibition by melatonin. Journal of Pineal Research, 62, e12370.

    Article  CAS  Google Scholar 

  22. Pandi-Perumal, S. R., BaHammam, A. S., Ojike, N. I., Akinseye, O. A., Kendzerska, T., Buttoo, K., et al. (2017). Melatonin and human cardiovascular disease. Journal of Cardiovascular Pharmacology and Therapeutics, 22, 122–132.

    Article  CAS  PubMed  Google Scholar 

  23. Brown, D. R., Samsa, L. A., Qian, L., & Liu, J. (2016). Advances in the study of heart development and disease using zebrafish. Journal of Cardiovascular Development and Disease, 3(2), 13.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Renier, C., Faraco, J. H., Bourgin, P., Motley, T., Bonaventure, P., Rosa, F., et al. (2007). Genomic and functional conservation of sedative-hypnotic targets in the zebrafish. Pharmacogenetics and Genomics, 17, 237–253.

    Article  CAS  PubMed  Google Scholar 

  25. Zhu, J.-J., Xu, Y.-Q., He, J.-H., Yu, H.-P., Huang, C.-J., Gao, J.-M., et al. (2014). Human cardiotoxic drugs delivered by soaking and microinjection induce cardiovascular toxicity in zebrafish: Zebrafish model for assessing drug-induced cardiovascular toxicity. Journal of Applied Toxicology, 34, 139–148.

    Article  CAS  PubMed  Google Scholar 

  26. Haverinen, J., & Vornanen, M. (2016). Deltamethrin is toxic to the fish (crucian carp, Carassius carassius) heart. Pesticide Biochemistry and Physiology, 129, 36–42.

    Article  CAS  PubMed  Google Scholar 

  27. Zhang, S., Xu, J., Kuang, X., Li, S., Li, X., Chen, D., et al. (2017). Biological impacts of glyphosate on morphology, embryo biomechanics and larval behavior in zebrafish (Danio rerio). Chemosphere, 181, 270–280.

    Article  CAS  PubMed  Google Scholar 

  28. Haverinen, J., Hassinen, M., Korajoki, H., & Vornanen, M. (2018). Cardiac voltage-gated sodium channel expression and electrophysiological characterization of the sodium current in the zebrafish (Danio rerio) ventricle. Progress in Biophysics and Molecular Biology, 138, 59–68.

    Article  CAS  PubMed  Google Scholar 

  29. Hoage, T., Ding, Y., & Xu, X. (2012). Quantifying cardiac functions in embryonic and adult zebrafish. In X. Peng & M. Antonyak (Eds.), Cardiovascular development: Methods and protocols, methods in molecular biology (pp. 11–20). Totowa, NJ: Humana Press.

    Chapter  Google Scholar 

  30. Poss, K. D., Keating, M. T., & Nechiporuk, A. (2003). Tales of regeneration in zebrafish. Developmental Dynamics, 226, 202–210.

    Article  PubMed  Google Scholar 

  31. Chopra, S. S., Stroud, D. M., Watanabe, H., Bennett, J. S., Burns, C. G., Wells, K. S., et al. (2010). Voltage-gated sodium channels are required for heart development in zebrafish. Circulation Research, 106, 1342–1350.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Chueh, T. C., Hsu, L. S., Kao, C. M., Hsu, T. W., Liao, H. Y., Wang, K. Y., et al. (2017). Transcriptome analysis of zebrafish embryos exposed to deltamethrin. Environmental Toxicology, 32, 1548–1557.

    Article  CAS  PubMed  Google Scholar 

  33. Gorge, G., & Nagel, R. (1990). Toxicity of lindane, atrazine, and deltamethrin to early life stages of zebrafish (Brachydanio rerio). Ecotoxicology and Environmental Safety, 20, 246–255.

    Article  CAS  PubMed  Google Scholar 

  34. Novak, A. E., Taylor, A. D., Pineda, R. H., Lasda, E. L., Wright, M. A., & Ribera, A. B. (2006). Embryonic and larval expression of zebrafish voltage-gated sodium channel α-subunit genes. Developmental Dynamics, 235, 1962–1973.

    Article  CAS  PubMed  Google Scholar 

  35. Papadatos, G. A., Wallerstein, P. M. R., Head, C. E. G., Ratcliff, R., Brady, P. A., Benndorf, K., et al. (2002). Slowed conduction and ventricular tachycardia after targeted disruption of the cardiac sodium channel gene Scn5a. Proceedings of the National academy of Sciences of the United States of America, 99, 6210–6215.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Balci, M. M., & Akdemir, R. (2011). NKX2.5 mutations and congenital heart disease: Is it a marker of cardiac anomalies? International Journal of Cardiology, 147, e44–45.

    Article  PubMed  Google Scholar 

  37. Zhou, P., He, A., & Pu, W. T. (2012). Regulation of GATA4 transcriptional activity in cardiovascular development and disease. Current Topics in Developmental Biology, 100, 143–169.

    Article  CAS  PubMed  Google Scholar 

  38. Yeung, H.-M., Hung, M.-W., Lau, C.-F., & Fung, M.-L. (2015). Cardioprotective effects of melatonin against myocardial injuries induced by chronic intermittent hypoxia in rats. Journal of Pineal Research, 58, 12–25.

    Article  CAS  PubMed  Google Scholar 

  39. Zheng, J., Yu, Y., Feng, W., Li, J., Liu, J., Zhang, C., et al. (2019). Influence of nanomolar deltamethrin on the hallmarks of primary cultured cortical neuronal network and the role of ryanodine receptors. Environmental Health Perspectives, 127, 67003.

    Article  PubMed  Google Scholar 

  40. Zhdanova, I. V., Wang, S. Y., Leclair, O. U., & Danilova, N. P. (2001). Melatonin promotes sleep-like state in zebrafish. Brain Research, 903, 263–268.

    Article  CAS  PubMed  Google Scholar 

  41. Appelbaum, L., Wang, G. X., Maro, G. S., Mori, R., Tovin, A., Marin, W., et al. (2009). Sleep–wake regulation and hypocretin–melatonin interaction in zebrafish. Proceedings of the National Academy of Sciences of the United States of America, 106, 21942–21947.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Appelbaum, L., Vallone, D., Anzulovich, A., Ziv, L., Tom, M., Foulkes, N. S., et al. (2006). Zebrafish arylalkylamine-N-acetyltransferase genes—Targets for regulation of the circadian clock. Journal of Molecular Endocrinology, 36, 337–347.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

X. Z. F and X. Y. L. conceived and designed experiments. Q. G. performed in situ hybridization and qRT-PCR. Z. Y. F. and X. L. carried out the surface tension test. X. Y. L. performed all other experiments. X. L. and Q. G., performed data analysis. X. L. drafted the manuscript, Y. Q. T. made important contributions to the discussion, and all author commented on the manuscript.

Funding

This project was initiated in the State Key Laboratory of Medicinal Chemical Biology at Nankai University. This work was supported by the Special Fund for Basic Research on Scientific Instruments of the Chinese National Natural Science Foundation [Grant No: 61633012], and the National Basic Research Program (973 program) of China [Grant No: 2015CB856500].

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Author notes

  1. **ngyu Liu, Qian Gao and Yaqiu Tang have contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Medicinal Chemical Biology, The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tian**, 300071, China

    **ngyu Liu, Yaqiu Tang & **zeng Feng

  2. Tian** Key Laboratory of Molecular Drug Research, College of Pharmacy, Nankai University, Tian**, 300071, China

    Qian Gao & Dongyan Chen

  3. The Institute of Robotics and Automatic Information Systems, College of Artificial Intelligence, Nankai University, Tian**, 300071, China

    Zeyang Feng & **n Zhao

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  1. **ngyu Liu
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Liu, X., Gao, Q., Feng, Z. et al. Protective Effects of Spermidine and Melatonin on Deltamethrin-Induced Cardiotoxicity and Neurotoxicity in Zebrafish. Cardiovasc Toxicol 21, 29–41 (2021). https://doi.org/10.1007/s12012-020-09591-5

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