Advertisement

Current Medical Science

, Volume 39, Issue 1, pp 21–27 | Cite as

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

  • Hong-yan Luo
  • Jacob Masika
  • Xiu-wen Guan
  • Li Nie
  • Dong-hui Ao
  • Yu Qi
  • Rui Shi
  • Jürgen Hescheler
  • Ying ZengEmail author
Article
  • 6 Downloads

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.

Key words

pyrethroid deltamethrin embryonic cardiomyocytes action potential developmental cardiotoxicity 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 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):742–748CrossRefGoogle Scholar
  2. 2.
    Demoute J. A brief review of the environmental fate and metabolism of pyrethroids. Pestic Sci, 1989,27:375–385CrossRefGoogle Scholar
  3. 3.
    Soderlund DM, Clark JM, Sheets LP, et al. Mechanisms of pyrethroid neurotoxicity: implications for cumulative risk assessment. Toxicology, 2002,171(1):3–59CrossRefGoogle Scholar
  4. 4.
    Ray DE, Fry JR. A reassessment of the neurotoxicity of pyrethroid insecticides. Pharmacol Ther, 2006,111(1): 174–193CrossRefGoogle Scholar
  5. 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):186–190CrossRefGoogle Scholar
  6. 6.
    Shafer TJ, Meyer DA, Crofton KM. Developmental neurotoxicity of pyrethroid insecticides: critical review and future research needs. Environ Health Perspect, 2005,113(2):123–136CrossRefGoogle Scholar
  7. 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):1145–1153CrossRefGoogle Scholar
  8. 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):383–389CrossRefGoogle Scholar
  9. 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, 2012,47:80–85CrossRefGoogle Scholar
  10. 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):116–122CrossRefGoogle Scholar
  11. 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):902–917CrossRefGoogle Scholar
  12. 12.
    Barker DJ. The fetal and infant origins of adult disease. BMJ, 1990,301(6761):1111CrossRefGoogle Scholar
  13. 13.
    Groom A, Elliott HR, Embleton ND, et al. Epigenetics and child health: basic principles. Arch Dis Child, 2011,96(9):863–869CrossRefGoogle Scholar
  14. 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):761–772CrossRefGoogle Scholar
  15. 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):119–124CrossRefGoogle Scholar
  16. 16.
    Vaiserman A. Early-life origin of adult disease: evidence from natural experiments. Exp Gerontol, 2011,46(2–3):189–192CrossRefGoogle Scholar
  17. 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):771–776CrossRefGoogle Scholar
  18. 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):605–610CrossRefGoogle Scholar
  19. 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):405–413CrossRefGoogle Scholar
  20. 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):498–501Google Scholar
  21. 21.
    Cantalamessa F. Acute toxicity of two pyrethroids, permethrin, and cypermethrin in neonatal and adult rats. Arch Toxicol, 1993,67(7):510–513CrossRefGoogle Scholar
  22. 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):148–156CrossRefGoogle Scholar
  23. 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):614–620CrossRefGoogle Scholar
  24. 24.
    Shi X, Gu A, Ji G, et al. Developmental toxicity of cypermethrin in embryo-larval stages of zebrafish. Chemosphere, 2011,85(6):1010–1016CrossRefGoogle Scholar
  25. 25.
    Abdel-Khalik MM, Hanafy MS, Abdel-Aziz MI. Studies on the teratogenic effects of deltamethrin in rats. Dtsch Tierarztl Wochenschr, 1993,100(4):142–143Google Scholar
  26. 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):165–171CrossRefGoogle Scholar
  27. 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):721–728CrossRefGoogle Scholar
  28. 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):413–420CrossRefGoogle Scholar
  29. 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):2964–2985CrossRefGoogle Scholar
  30. 30.
    Casida JE, Durkin KA. Neuroactive insecticides: targets, selectivity, resistance, and secondary effects. Annu Rev Entomol, 2013,58:99–117CrossRefGoogle Scholar
  31. 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):877–888CrossRefGoogle Scholar
  32. 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):266–272CrossRefGoogle Scholar
  33. 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, 2012,48:109–120CrossRefGoogle Scholar
  34. 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):693–700CrossRefGoogle Scholar
  35. 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):403–412CrossRefGoogle Scholar
  36. 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):1171–1191CrossRefGoogle Scholar
  37. 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):1067–1082Google Scholar
  38. 38.
    Belardinelli L, Antzelevitch C, Vos MA. Assessing predictors of drug–induced torsade de pointes. Trends Pharmacol Sci, 2003,24(12):619–625CrossRefGoogle Scholar
  39. 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):323–331CrossRefGoogle Scholar
  40. 40.
    Denac H, Mevissen M, Scholtysik G. Structure, function and pharmacology of voltage–gated sodium channels. Naunyn Schmiedebergs Arch Pharmacol, 2000,362(6):453–479CrossRefGoogle Scholar
  41. 41.
    Honerjäger P. Cardioactive substances that prolong the open state of sodium channels. Rev Physiol Biochem Pharmacol, 1982,92:1–74Google Scholar
  42. 42.
    Bennett PB, Yazawa K, Makita N, et al. Molecular mechanism for an inherited cardiac arrhythmia. Nature, 1995, 376(6542):683–685CrossRefGoogle Scholar
  43. 43.
    Wang Q, Shen J, Splawski I, et al. SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell, 1995,80(5):805–811CrossRefGoogle Scholar
  44. 44.
    January CT, Riddle JM. Early afterdepolarizations: mechanism of induction and block. A role for L–type Ca2+ current. Circ Res, 1989,64(5):977–990CrossRefGoogle Scholar
  45. 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):458–466CrossRefGoogle Scholar
  46. 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):186–190CrossRefGoogle Scholar
  47. 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):560–567CrossRefGoogle Scholar
  48. 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):472–481CrossRefGoogle Scholar
  49. 49.
    Agarwal DK, Chauhan LK, Gupta SK, et al. Cytogenetic effects of deltamethrin on rat bone marrow. Mutat Res, 1994, 311(1):133–138CrossRefGoogle Scholar
  50. 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):235–243CrossRefGoogle Scholar
  51. 51.
    Richardson JR, Taylor MM, Shalat SL, et al. Developmental pesticide exposure reproduces features of attention deficit hyperactivity disorder. FASEB J, 2015,29(5):1960–1972CrossRefGoogle Scholar

Copyright information

© Huazhong University of Science and Technology 2019

Authors and Affiliations

  • Hong-yan Luo
    • 1
    • 2
  • Jacob Masika
    • 1
    • 2
    • 3
  • Xiu-wen Guan
    • 4
  • Li Nie
    • 1
    • 2
    • 5
  • Dong-hui Ao
    • 1
    • 2
  • Yu Qi
    • 1
    • 2
  • Rui Shi
    • 1
    • 2
  • Jürgen Hescheler
    • 6
  • Ying Zeng
    • 7
    Email author
  1. 1.Department of Physiology, Hubei Key Laboratory of Drug Target Research and Pharmacodynamic EvaluationHuazhong University of Science and TechnologyWuhanChina
  2. 2.School of Basic Medicine, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  3. 3.Department of Medical Physiology, Faculty of Health SciencesEgerton UniversityNjoroKenya
  4. 4.The People’s Hospital of Huangpi DistrictWuhanChina
  5. 5.College of PharmacyWuhan Institute of BioengineeringWuhanChina
  6. 6.Institute of PhysiologyUniversity of CologneCologneGermany
  7. 7.Department of Pharmaceutics, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

Personalised recommendations