Skip to main content
SpringerLink
Log in

Long Term Perinatal Deltamethrin Exposure Alters Electrophysiological Properties of Embryonic Ventricular Cardiomyocyte

  • Published:
Current Medical Science Aims and scope Submit manuscript

Abstract

Increased use of pyrethroids and the exposure to pyrethroids for pregnant women and children have raised the concerns over the potential effect of pyrethroids on developmental cardiotoxicity and other abnormalities. The purpose of this study was to investigate whether long term perinatal deltamethrin exposure altered embryonic cardiac electrophysiology in mice. Pregnant mice were administered with 0 or 3 mg/kg of deltamethrin by gavage daily from gestational day (gd) 10.5 to gd 17. 5. Whole cell patch-clamp technique was used in electrophysiological study, and real time RT-PCR was applied to analyze the molecular changes for the electrophysiological properties. Deltamethrin exposure resulted in increased mortality of pregnant mice and decreased viability of embryos. Moreover, deltamethrin slowed the maximum depolarization velocity (Vmax), prolonged the action potential duration (APD) and depolarized the maximum diastolic potential (MDP) of embryonic cardiomyocytes. Additionally, perinatal deltamethrin exposure decreased the mRNA expression of Na+ channel regulatory subunit Navβ1, inward rectifier K+ channel subunit Kir2.1, and delayed rectifier K+ channel subunit MERG while the L-type Ca2+ channel subunit, Cav1.2 expression was increased. On the contrary, deltamethrin administration did not significantly alter the regulation of β-adrenergic or muscarinic receptor on embryonic cardiomyocytes. In conclusion, deltamethrin exposure at perinatal stage significantly alters mRNA expression of embryonic cardiac ion channels and therefore influences embryonic cardiac electrophysiological properties. This highlights the need to understand the persistent effects of pyrethroid exposure on cardiac function during embryonic development due to potential for cardiac arrhythmogenicity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Barr DB, Olsson AO, Wong LY, et al. Urinary concentrations of metabolites of pyrethroid insecticides in the general U.S. population: National Health and Nutrition Examination Survey 1999–2002. Environ Health Perspect, 2010,118 (6):742–748

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Demoute J. A brief review of the environmental fate and metabolism of pyrethroids. Pestic Sci, 1989,27:375–385

    Article  CAS  Google Scholar 

  3. Soderlund DM, Clark JM, Sheets LP, et al. Mechanisms of pyrethroid neurotoxicity: implications for cumulative risk assessment. Toxicology, 2002,171(1):3–59

    Article  CAS  PubMed  Google Scholar 

  4. Ray DE, Fry JR. A reassessment of the neurotoxicity of pyrethroid insecticides. Pharmacol Ther, 2006,111(1): 174–193

    Article  CAS  PubMed  Google Scholar 

  5. Sheets LP, Doherty JD, Law MW, et al. Age-dependent differences in the susceptibility of rats to deltamethrin. Toxicol Appl Pharmacol, 1994,126(1):186–190

    Article  CAS  PubMed  Google Scholar 

  6. Shafer TJ, Meyer DA, Crofton KM. Developmental neurotoxicity of pyrethroid insecticides: critical review and future research needs. Environ Health Perspect, 2005,113(2):123–136

    Article  CAS  PubMed  Google Scholar 

  7. Naeher LP, Tulve NS, Egeghy PP, et al. Organophosphorus and pyrethroid insecticide urinary metabolite concentrations in young children living in a southeastern United States city. Sci Total Environ, 2010,408(5):1145–1153

    Article  CAS  PubMed  Google Scholar 

  8. Whyatt RM, Garfinkel R, Hoepner LA, et al. Withinand between-home variability in indoor-air insecticide levels during pregnancy among an inner-city cohort from New York City. Environ Health Perspect, 2007,115(3):383–389

    Article  CAS  PubMed  Google Scholar 

  9. Wickerham EL, Lozoff B, Shao J, et al. Reduced birth weight in relation to pesticide mixtures detected in cord blood of full-term infants. Environ Int, 2012,47:80–85

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ostrea EM, Bielawski DM, Posecion NC, et al. Combined analysis of prenatal (maternal hair and blood) and neonatal (infant hair, cord blood and meconium) matrices to detect fetal exposure to environmental pesticides. Environ Res, 2009,109(1):116–122

    Article  CAS  PubMed  Google Scholar 

  11. Bouwman H, Sereda B, Meinhardt HM. Simultaneous presence of DDT and pyrethroid residues in human breast milk from a malaria endemic area in South Africa. Environ Pollut, 2006,44(3):902–917

    Article  CAS  Google Scholar 

  12. Barker DJ. The fetal and infant origins of adult disease. BMJ, 1990,301(6761):1111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Groom A, Elliott HR, Embleton ND, et al. Epigenetics and child health: basic principles. Arch Dis Child, 2011,96(9):863–869

    Article  CAS  PubMed  Google Scholar 

  14. Novotny J, Bourova L, Malkova O, et al. G proteins, betaadrenoreceptors and beta-adrenergic responsiveness in immature and adult rat ventricular myocardium: influence of neonatal hypo-and hyperthyroidism. J Mol Cell Cardiol, 1999,31(4):761–772

    Article  CAS  PubMed  Google Scholar 

  15. Oliveira Ldos S, da Silva LP, da Silva AI, et al. Effects of early weaning on the circadian rhythm and behavioral satiety sequence in rats. Behav Processes, 2011,86(1):119–124

    Article  PubMed  Google Scholar 

  16. Vaiserman A. Early-life origin of adult disease: evidence from natural experiments. Exp Gerontol, 2011,46(2–3):189–192

    Article  PubMed  Google Scholar 

  17. Chanda SM, Pope CN. Neurochemical and neurobehavioral effects of repeated gestational exposure to chlorpyrifos in maternal and developing rats. Pharmacol Biochem Behav, 1996,53(4):771–776

    Article  CAS  PubMed  Google Scholar 

  18. Doucet J, Tague B, Arnold DL, et al. Persistent organic pollutant residues in human fetal liver and placenta from Greater Montreal, Quebec: a longitudinal study from 1998 through 2006. Environ Health Perspect, 2009,117(4):605–610

    Article  CAS  PubMed  Google Scholar 

  19. Gupta RC, Rech RH, Lovell KL, et al. Brain cholinergic, behavioral, and morphological development in rats exposed in utero to methylparathion. Toxicol Appl Pharmacol, 1985,77(3):405–413

    Article  CAS  PubMed  Google Scholar 

  20. Muto MA, Lobelle F, Bidanset JH, et al. Embryotoxicity and neurotoxicity in rats associated with prenatal exposure to DURSBAN. Vet Hum Toxicol, 1992,34(6):498–501

    CAS  PubMed  Google Scholar 

  21. Cantalamessa F. Acute toxicity of two pyrethroids, permethrin, and cypermethrin in neonatal and adult rats. Arch Toxicol, 1993,67(7):510–513

    Article  CAS  PubMed  Google Scholar 

  22. Bell EM, Hertz-Picciotto I, Beaumont JJ. A case-control study of pesticides and fetal death due to congenital anomalies. Epidemiology, 2001,12(2):148–156

    Article  CAS  PubMed  Google Scholar 

  23. Hanke W, Romitti P, Fuortes L, et al. The use of pesticides in a Polish rural population and its effect on birth weight. Int Arch Occup Environ Health, 2003,76(8):614–620

    Article  PubMed  Google Scholar 

  24. Shi X, Gu A, Ji G, et al. Developmental toxicity of cypermethrin in embryo-larval stages of zebrafish. Chemosphere, 2011,85(6):1010–1016

    Article  CAS  PubMed  Google Scholar 

  25. Abdel-Khalik MM, Hanafy MS, Abdel-Aziz MI. Studies on the teratogenic effects of deltamethrin in rats. Dtsch Tierarztl Wochenschr, 1993,100(4):142–143

    CAS  PubMed  Google Scholar 

  26. Armstrong LE, Driscoll MV, Donepudi AC, et al. Effects of developmental deltamethrin exposure on white adipose tissue gene expression. J Biochem Mol Toxicol, 2013,27(2):165–171

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Caudle WM, Richardson JR, Wang M, et al. Perinatal heptachlor exposure increases expression of presynaptic dopaminergic markers in mouse striatum. Neurotoxicology, 2005,26(4):721–728

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Liu A, Tang M, Xi J, et al. Functional characterization of inward rectifier potassium ion channel in murine fetal ventricular cardiomyocytes. Cell Physiol Biochem, 2010,26(3):413–420

    Article  CAS  PubMed  Google Scholar 

  29. Morgan MK. Children’s exposures to pyrethroid insecticides at home: a review of data collected in published exposure measurement studies conducted in the United States. Int J Environ Res Public Health, 2012,9(8):2964–2985

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Casida JE, Durkin KA. Neuroactive insecticides: targets, selectivity, resistance, and secondary effects. Annu Rev Entomol, 2013,58:99–117

    Article  CAS  PubMed  Google Scholar 

  31. Vais H, Williamson MS, Devonshire AL, et al. The molecular interactions of pyrethroid insecticides with insect and mammalian sodium channels. Pest Manag Sci, 2001,57(10):877–888

    Article  CAS  PubMed  Google Scholar 

  32. Du Y, Nomura Y, Luo N, et al. Molecular determinants on the insect sodium channel for the specific action of type II pyrethroid insecticides. Toxicol Appl Pharmacol, 2009,234(2):266–272

    Article  CAS  PubMed  Google Scholar 

  33. Babina K, Dollard M, Pilotto L, et al. Environmental exposure to organophosphorus and pyrethroid pesticides in South Australian preschool children: a cross sectional study. Environ Int, 2012,48:109–120

    Article  CAS  PubMed  Google Scholar 

  34. Fahmi A, Patel M, Stevens EB, et al. The sodium channel beta–subunit SCN3b modulates the kinetics of SCN5a and is expressed heterogeneously in sheep heart. J Physiol, 2001,537(Pt 3):693–700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Ko SH, Lenkowski PW, Lee HC, et al. Modulation of Na(v)1.5 by beta1––and beta3–subunit co–expression in mammalian cells. Pflugers Arch, 2005,449(4):403–412

    Article  CAS  PubMed  Google Scholar 

  36. Nuss HB, Chiamvimonvat N, Perez–Garcia MT, et al. Functional association of the beta 1 subunit with human cardiac (hH1) and rat skeletal muscle (mu 1) sodium channel alpha subunits expressed in Xenopus oocytes. J Gen Physiol, 1995,106(6):1171–1191

    Article  CAS  PubMed  Google Scholar 

  37. Spencer CI, Yuill KH, Borg JJ, et al. Actions of pyrethroid insecticides on sodium currents, action potentials, and contractile rhythm in isolated mammalian ventricular myocytes and perfused hearts. J Pharmacol Exp Ther, 2001,98(3):1067–1082

    Google Scholar 

  38. Belardinelli L, Antzelevitch C, Vos MA. Assessing predictors of drug–induced torsade de pointes. Trends Pharmacol Sci, 2003,24(12):619–625

    Article  CAS  PubMed  Google Scholar 

  39. Restivo M, Caref EB, Kozhevnikov DO, et al. Spatial dispersion of repolarization is a key factor in the arrhythmogenicity of long QT syndrome. J Cardiovasc Electrophysiol, 2004,15(3):323–331

    Article  PubMed  Google Scholar 

  40. Denac H, Mevissen M, Scholtysik G. Structure, function and pharmacology of voltage–gated sodium channels. Naunyn Schmiedebergs Arch Pharmacol, 2000,362(6):453–479

    Article  CAS  PubMed  Google Scholar 

  41. Honerjäger P. Cardioactive substances that prolong the open state of sodium channels. Rev Physiol Biochem Pharmacol, 1982,92:1–74

    PubMed  Google Scholar 

  42. Bennett PB, Yazawa K, Makita N, et al. Molecular mechanism for an inherited cardiac arrhythmia. Nature, 1995, 376(6542):683–685

    Article  CAS  Google Scholar 

  43. Wang Q, Shen J, Splawski I, et al. SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell, 1995,80(5):805–811

    Article  CAS  PubMed  Google Scholar 

  44. January CT, Riddle JM. Early afterdepolarizations: mechanism of induction and block. A role for L–type Ca2+ current. Circ Res, 1989,64(5):977–990

    Article  CAS  PubMed  Google Scholar 

  45. Kaseda S, Gilmour RF Jr, Zipes DP. Depressant effect of magnesium on early afterdepolarizations and triggered activity induced by cesium, quinidine, and 4–aminopyridine in canine cardiac Purkinje fibers. Am Heart J, 1989,118(3):458–466

    Article  CAS  PubMed  Google Scholar 

  46. Sheets LP, Doherty JD, Law MW, et al. Age–dependent differences in the susceptibility of rats to deltamethrin. Toxicol Appl Pharmacol, 1994,26(1):186–190

    Article  Google Scholar 

  47. Farag AT, Goda NF, Shaaban NA, et al. Effects of oral exposure of synthetic pyrethroid, cypermethrin on the behavior of F1–progeny in mice. Reprod Toxicol, 2007,23(4):560–567

    Article  CAS  PubMed  Google Scholar 

  48. Sinha C, Seth K, Islam F, et al. Behavioral and neurochemical effects induced by pyrethroid–based mosquito repellent exposure in rat offsprings during prenatal and early postnatal period. Neurotoxicol Teratol, 2006,28(4):472–481

    Article  CAS  PubMed  Google Scholar 

  49. Agarwal DK, Chauhan LK, Gupta SK, et al. Cytogenetic effects of deltamethrin on rat bone marrow. Mutat Res, 1994, 311(1):133–138

    Article  CAS  PubMed  Google Scholar 

  50. Kung TS, Richardson JR, Cooper KR, et al. Developmental Deltamethrin Exposure Causes Persistent Changes in Dopaminergic Gene Expression, Neurochemistry, and Locomotor Activity in Zebrafish. Toxicol Sci, 2015,146(2):235–243

    Article  PubMed  PubMed Central  Google Scholar 

  51. Richardson JR, Taylor MM, Shalat SL, et al. Developmental pesticide exposure reproduces features of attention deficit hyperactivity disorder. FASEB J, 2015,29(5):1960–1972

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Author notes

  1. The authors contributed equally to this study.

Authors and Affiliations

  1. Department of Physiology, Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Huazhong University of Science and Technology, Wuhan, 430030, China

    Hong-yan Luo, Jacob Masika, Li Nie, Dong-hui Ao, Yu Qi & Rui Shi

  2. School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Hong-yan Luo, Jacob Masika, Li Nie, Dong-hui Ao, Yu Qi & Rui Shi

  3. Department of Medical Physiology, Faculty of Health Sciences, Egerton University, Njoro, 535 20115, Kenya

    Jacob Masika

  4. The People’s Hospital of Huangpi District, Wuhan, 430300, China

    Xiu-wen Guan

  5. College of Pharmacy, Wuhan Institute of Bioengineering, Wuhan, 430415, China

    Li Nie

  6. Institute of Physiology, University of Cologne, Cologne, 50931, Germany

    Jürgen Hescheler

  7. Department of Pharmaceutics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Ying Zeng

Authors
  1. Hong-yan Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jacob Masika
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiu-wen Guan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Li Nie
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dong-hui Ao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yu Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rui Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jürgen Hescheler
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ying Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ying Zeng.

Additional information

This study was supported by a grant from the National Natural Science Foundation of China (No. 81100818).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Luo, Hy., Masika, J., Guan, Xw. et al. Long Term Perinatal Deltamethrin Exposure Alters Electrophysiological Properties of Embryonic Ventricular Cardiomyocyte. CURR MED SCI 39, 21–27 (2019). https://doi.org/10.1007/s11596-019-1995-5

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11596-019-1995-5

Key words

Search

Navigation