Skip to main content

Advertisement

Log in

Perturbation of Rat Heart Plasma Membrane Fluidity Due to Metabolites of Permethrin Insecticide

  • Published:
Cardiovascular Toxicology Aims and scope Submit manuscript

Abstract

Due to increased global use, acute and chronic exposures to pyrethroid insecticides in humans are of clinical concern. Pyrethroids have a primary mode of action that involves interference with the sodium and calcium channels in excitable cells, which may include cardiac myocytes. Here, we investigated the possible cardiac toxicity of permethrin metabolites (METP), 3-phenoxy-benzyl alcohol (3PBA), 3-phenoxy-benzaldehyde (3PBALD), and 3-phenoxybenzoic acid (3PBACID). Plasma membrane fluidity, polarity, lipid, and protein oxidation were studied in isolated rat heart cells. Laurdan was chosen as probe to detect the lateral mobility and polarity of its environment and thus water penetration into the hydrophobic part of the bilayer, while 1,6-diphenyl-1,3,5-hexatriene permits to measure changes in fluidity in the inner part of the bilayer. Results show that METP can change membrane fluidity at different depths of the bilayer according to their partition coefficient. Consequently, 3PBA, at all concentration used, decreases membrane fluidity and polarity in the hydrophilic–hydrophobic region of the bilayer, and similar effect was observed with 20 μM 3PBALD or 10 or 20 μM 3 PBACID. Membrane dynamics in the hydrophobic core resulted decreased by 3PBALD, while it was increased by 20 μM 3PBACID. All METP increase protein and lipid oxidation, and the peroxidative lipid damage decreases with the type of METP produced during the transformation pathway from parent compound to 3PBACID. Consequently, 3PBA induced the highest lipid peroxidation, while 3PBACID was the stronger inducer of protein damage.

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

Access this article

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

Instant access to the full article PDF.

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Bjørling-Poulsen, M. A. H., & Grandjean, P. (2008). Potential developmental neurotoxicity of pesticides used in Europe. Environmental Health, 22, 50–77.

    Article  Google Scholar 

  2. Williamson, M. S., Martinez-Torres, D., Hick, C. A., & Devonshire, A. L. (1996). Identification of mutations in the housefly para-type sodium channel gene associated with knock-down resistance (kdr) to pyrethroid insecticides. Molecular and General Genetics, 252, 51–60.

    Article  PubMed  CAS  Google Scholar 

  3. Aldridge, W. N. (1990). An assessment of the toxicological properties of pyrethroids and their neurotoxicity. Critical Reviews in Toxicology, 21, 89–104.

    Article  PubMed  CAS  Google Scholar 

  4. Bradberry, S. M., Proudfoot, A. T., & Vale, J. A. (2005). Poisoning due to pyrethroids. Toxicological Reviews, 24, 93–106.

    Article  PubMed  CAS  Google Scholar 

  5. Barr, D. B., Wong, O. A., Unubka, S., Baker, S. E., Whitehead, R. D., Magsumbol, M. S., et al. (2010). Urinary concentration of metabolites of pyrethroid insecticides in the general US population: National health and nutrition examination survey 1999–2002. Environment Health Perspectiv, 118, 742–748.

    Article  CAS  Google Scholar 

  6. Bouwman, H., & Kylin, H. (2009). Malaria control insecticide residues in breast milk: the need to consider infant health risks. Environmental Health Perspectives, 117, 1477–1480.

    PubMed  CAS  Google Scholar 

  7. McCarthy, A. R., Thomson, B. M., Shaw, I. C., & Abell, A. D. (2006). Estrogenicity of pyrethroid insecticide metabolites. Journal of Environmental Monitoring, 8, 197–202.

    Article  PubMed  CAS  Google Scholar 

  8. Saieva, C., Aprea, C., Tumino, R., Masala, G., Salvini, S., Frasca, G., et al. (2004). Twenty-four-hour urinary excretion of ten pesticide metabolites in healthy adults in two different areas of Italy (Florence and Ragusa). The Science of the Total Environment, 33, 271–280.

    Google Scholar 

  9. Nakamura, Y., Sugihara, K., Sone, T., Isobe, M., Ohta, S., & Kitamura, S. (2007). The in vitro metabolism of a pyrethroid insecticide, permethrin, and its hydrolysis products in rats. Toxicology, 235, 176–184.

    Article  PubMed  CAS  Google Scholar 

  10. Spencer, C. I., Yuill, K. H., Borg, J. J., Hancox, J. C., & Kozlowski, R. Z. (2001). Actions of pyrethroid insecticides on sodium currents, action potentials and contractile rhythm in isolated mammalian ventricular myocytes and perfused hearts. Journal of Pharmacology and Experimental Therapeutics, 298, 1067–1082.

    PubMed  CAS  Google Scholar 

  11. Ian Spencer, C., & Sham, S. K. J. (2005). Mechanisms underlying the effects of the pyrethroid tefluthrin on action potential duration in isolated rat ventricular myocytes. Journal of Pharmacological Experimental Therapy, 315, 16–23.

    Article  Google Scholar 

  12. Vadhana, M. S. D., Nasuti, C., & Gabbianelli, R. (2010). Purine bases oxidation and repair following permethrin insecticide treatment in rat heart cells. Cardiovascular Toxicology, 10, 199–207.

    Article  PubMed  Google Scholar 

  13. Lowry, O. H., Rosebrough, N. J., Farr, A. L., & Randall, R. L. (1951). Protein measurement with the folin phenol reagent. Journal of Biological Chemistry, 193, 265–275.

    PubMed  CAS  Google Scholar 

  14. Shinitzky, M., & Barenholz, Y. (1978). Fluidity parameters of lipid regions determined by fluorescence polarization. Biochimica et Biophysica Acta, 515, 367–394.

    PubMed  CAS  Google Scholar 

  15. Parasassi, T., Parasassi, G., De Stasio, A., D’Ubaldo, A., & Gratton, E. (1990). Phase fluctuation in phospholipid membranes revealed by Laurdan fluorescence. Biophysical Journal, 57, 1179–1186.

    Article  PubMed  CAS  Google Scholar 

  16. Parasassi, T., Parasassi, G., De Stasio, G., Ravagnan, R. M., & Gratton, E. (1991). Quantitation of lipid phases in phospholipids vesicles by the generalized polarization of Laurdan fluorescence. Biophysical Journal, 60, 179–189.

    Article  PubMed  CAS  Google Scholar 

  17. Lenz, A. G., Costabel, U., Shaltiel, S., & Levine, R. L. (1989). Determination of carbonyl groups in oxidatively modified proteins by reduction with tritiated sodium borohydride. Analytical Biochemistry, 177(2), 419–425.

    Article  PubMed  CAS  Google Scholar 

  18. MarkCullen, R. (2009). Invited commentary: The search for preventable causes of cardiovascular disease—Whither work? American Journal of Epidemiology, 169, 1422–1425.

    Article  Google Scholar 

  19. MacDonald, L. A., Cohen, A., Baron, S., & Burchfiel, C. M. (2009). Search for preventable causes of cardiovascular disease. American Journal of Epidemiology, 169, 1426–1427.

    Article  PubMed  Google Scholar 

  20. Hildebrand, E. M., McRory, J. E., Snutch, T. P., & Stea, A. (2004). Mammalian, voltage-gated calcium channels are potently blocked by the pyrethroid insecticide allethrin. Journal Pharmacologicl Experimental Therapy, 308, 805–813.

    Article  CAS  Google Scholar 

  21. Forshaw, P. J., & Bradbury, J. E. (1983). Pharmacological effects of pyrethroids on the cardiovascular system of the rat. European Journal of Pharmacology, 91(2–3), 207–213.

    Article  PubMed  CAS  Google Scholar 

  22. Berlin, J. R., Akera, T., Brody, T. M., & Matsumura, F. (1984). The inotropic effects of a synthetic pyrethroid decamethrin on isolated guinea pig atrial muscle. European Journal of Pharmacology, 98, 313–322.

    Article  PubMed  CAS  Google Scholar 

  23. Gabbianelli, R., Falcioni, G., Nasuti, C., & Cantalamessa, F. (2002). Cypermethrin-induced plasma membrane perturbation on erythrocytes from rats: reduction of fluidity in the hydrophobic core and in glutathione peroxidase activity. Toxicology, 175, 91–101.

    Article  PubMed  CAS  Google Scholar 

  24. Gabbianelli, R., Nasuti, C., Falcioni, G., & Cantalamessa, F. (2004). Lymphocyte DNA damage in rats exposed to pyrethroids: Effect of supplementation with vitamins E and C. Toxicology, 203, 17–26.

    Article  PubMed  CAS  Google Scholar 

  25. Gabbianelli, R., Falcioni, M. L., Nasuti, C., Cantalamessa, F., Imada, I., & Inoue, M. (2009). Effect of permethrin insecticide on rat polymorphonuclear neutrophils. Chemistry of Biological Interaction, 182, 245–252.

    Article  CAS  Google Scholar 

  26. Gabbianelli, R., Falcioni, M. L., Cantalamessa, F., & Nasuti, C. (2009). Permethrin induces lymphocyte DNA lesions at both Endo III and Fpg sites and changes in monocyte respiratory burst in rats. Journal of Applied Toxicology, 29, 317–322.

    Article  PubMed  CAS  Google Scholar 

  27. Nasuti, C., Cantalamessa, F., Falcioni, G., & Gabbianelli, R. (2003). Different effects of type I and type II pyrethroids on erythrocyte plasma membrane properties and enzymatic activity in rats. Toxicology, 191, 233–244.

    Article  PubMed  CAS  Google Scholar 

  28. Nasuti, C., Gabbianelli, R., Falcioni, M. L., Di Stefano, A., Sozio, P., & Cantalamessa, F. (2007). Dopaminergic system modulation, behavioural changes, and oxidative stress after neonatal administration of pyrethroids. Toxicol, 229, 194–205.

    Article  CAS  Google Scholar 

  29. Nasuti, C., Falcioni, M. L., Nwankwo, I. E., Cantalamessa, F., & Gabbianelli, R. (2008). Effect of permethrin plus antioxidants on locomotor activity and striatum in adolescent rats. Toxicology, 25, 45–50.

    Article  Google Scholar 

  30. Zhang, Y., Zhao, M., Jin, M., Xu, C., Wang, C., & Liu, W. (2010). Immunotoxicity of pyrethroid metabolites in an in vitro model. Environmental Toxicology and Chemistry, 29, 2505–2510.

    Article  PubMed  CAS  Google Scholar 

  31. Taylor, J. S., Thomson, B. M., Lang, C. N., Sin, F. Y. T., & Podivinsky, E. (2010). Etrogenic pyrethroid pesticides regulate expression of estrogen receptor transcripts in mouse sertoli cells differently from 17β-estradiol. Journal of Toxicology and Environmental Health, Part A, 73, 1075–1089.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This paper was supported by National Grant (N° 2008ZW3FJ3) supported by MIUR to R.G.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rosita Gabbianelli.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vadhana, D., Carloni, M., Fedeli, D. et al. Perturbation of Rat Heart Plasma Membrane Fluidity Due to Metabolites of Permethrin Insecticide. Cardiovasc Toxicol 11, 226–234 (2011). https://doi.org/10.1007/s12012-011-9116-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12012-011-9116-0

Keywords

Navigation