Skip to main content
Top
Published in: Cardiovascular Toxicology 1/2021

01-01-2021

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

Authors: Xingyu Liu, Qian Gao, Zeyang Feng, Yaqiu Tang, Xin Zhao, Dongyan Chen, Xizeng Feng

Published in: Cardiovascular Toxicology | Issue 1/2021

Login to get access

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 looping, 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.
Appendix
Available only for authorised users
Literature
1.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
2.
go back to reference Soderlund, D. M. (2012). Molecular mechanisms of pyrethroid insecticide neurotoxicity: Recent advances. Archives of Toxicology, 86, 165–181.PubMedCrossRef Soderlund, D. M. (2012). Molecular mechanisms of pyrethroid insecticide neurotoxicity: Recent advances. Archives of Toxicology, 86, 165–181.PubMedCrossRef
3.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
4.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
5.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
6.
go back to reference 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.PubMedPubMedCentralCrossRef 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.PubMedPubMedCentralCrossRef
7.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
8.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
9.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
10.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
11.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
12.
go back to reference 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. 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.
13.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
14.
go back to reference Raina, A., & Jänne, J. (1975). Physiology of the natural polyamines putrescine, spermidine and spermine. Medicine and Biology, 53, 121–147. Raina, A., & Jänne, J. (1975). Physiology of the natural polyamines putrescine, spermidine and spermine. Medicine and Biology, 53, 121–147.
15.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
16.
go back to reference 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.PubMedPubMedCentralCrossRef 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.PubMedPubMedCentralCrossRef
17.
go back to reference Sharma, S., Kumar, P., & Deshmukh, R. (2018). Neuroprotective potential of spermidine against rotenone induced Parkinson's disease in rats. Neurochemistry International, 116, 104–111.PubMedCrossRef Sharma, S., Kumar, P., & Deshmukh, R. (2018). Neuroprotective potential of spermidine against rotenone induced Parkinson's disease in rats. Neurochemistry International, 116, 104–111.PubMedCrossRef
18.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
19.
go back to reference 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.CrossRef 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.CrossRef
20.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
21.
go back to reference 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.CrossRef 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.CrossRef
22.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
23.
go back to reference 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.PubMedPubMedCentralCrossRef 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.PubMedPubMedCentralCrossRef
24.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
25.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
26.
go back to reference Haverinen, J., & Vornanen, M. (2016). Deltamethrin is toxic to the fish (crucian carp, Carassius carassius) heart. Pesticide Biochemistry and Physiology, 129, 36–42.PubMedCrossRef Haverinen, J., & Vornanen, M. (2016). Deltamethrin is toxic to the fish (crucian carp, Carassius carassius) heart. Pesticide Biochemistry and Physiology, 129, 36–42.PubMedCrossRef
27.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
28.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
29.
go back to reference 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.CrossRef 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.CrossRef
30.
go back to reference Poss, K. D., Keating, M. T., & Nechiporuk, A. (2003). Tales of regeneration in zebrafish. Developmental Dynamics, 226, 202–210.PubMedCrossRef Poss, K. D., Keating, M. T., & Nechiporuk, A. (2003). Tales of regeneration in zebrafish. Developmental Dynamics, 226, 202–210.PubMedCrossRef
31.
go back to reference 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.PubMedPubMedCentralCrossRef 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.PubMedPubMedCentralCrossRef
32.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
33.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
34.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
35.
go back to reference 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.PubMedPubMedCentralCrossRef 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.PubMedPubMedCentralCrossRef
36.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
37.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
38.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
39.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
40.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
41.
go back to reference 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.PubMedPubMedCentralCrossRef 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.PubMedPubMedCentralCrossRef
42.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
Metadata
Title
Protective Effects of Spermidine and Melatonin on Deltamethrin-Induced Cardiotoxicity and Neurotoxicity in Zebrafish
Authors
Xingyu Liu
Qian Gao
Zeyang Feng
Yaqiu Tang
Xin Zhao
Dongyan Chen
Xizeng Feng
Publication date
01-01-2021
Publisher
Springer US
Published in
Cardiovascular Toxicology / Issue 1/2021
Print ISSN: 1530-7905
Electronic ISSN: 1559-0259
DOI
https://doi.org/10.1007/s12012-020-09591-5

Other articles of this Issue 1/2021

Cardiovascular Toxicology 1/2021 Go to the issue