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Purine Bases Oxidation and Repair Following Permethrin Insecticide Treatment in Rat Heart Cells

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Abstract

Pollutants including insecticides have been recently reported to be a risk factor involved in various diseases. Permethrin, a member of the family of synthetic pyrethroids, is widely used as insecticide in agriculture and other domestic applications. To investigate possible cardiotoxicity, we had examined different concentrations of permethrin on the freshly isolated rat heart cells using the alkaline comet assay. A significant difference in % tail DNA between all concentrations of permethrin (5, 10, 20 μM) and vehicle (control) without enzymes and with Fpg-treated cells were measured. The results indicated that permethrin induced oxidative damage to purine bases in the heart cells. Pyrimidines oxidation was evaluated using Endonuclease III (Endo III), but the results did not reveal any significant changes. After permethrin exposure, cells were studied to evaluate their DNA repair capacity. A complete DNA repair at 10 and 20 μM was measured after 30 and 60 min of repair intervals. Significant change in plasma membrane fluidity at different depths of bilayer was measured following permethrin treatment. Membrane fluidity in the hydrophilic–hydrophobic region was reduced, while the hydrophobic inner resulted more fluid following permethrin treatment of heart cells. This work points to standardize conditions applicable to ex vivo cells following in vivo treatment in order to study the cardiotoxicity of insecticide.

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References

  1. Bradberry, S. M., Cage, S. A., Proudfoot, A. T., & Vale, J. A. (2005). Poisoning due to pyrethroids. Toxicological reviews, 24(2), 93–106.

    Article  CAS  PubMed  Google Scholar 

  2. Keikotlhaile, B. M., Spanoghea, P., & Steurbauta, W. (2010). Effects of food processing on pesticide residues in fruits and vegetables: A meta-analysis approach. Food and Chemical Toxicology, 48(1), 1–6.

    Article  CAS  PubMed  Google Scholar 

  3. Weston, D. P., You, J., & Lydy, M. J. (2004). Distribution and toxicity of sediment-associated pesticides in agricultural-dominated water bodies of California’s central valley. Environmental Science and Technology, 38(10), 2752–2759.

    Article  CAS  PubMed  Google Scholar 

  4. Agnihotri, N.P. (1999) Pesticide safety evaluation and monitoring (pp.13–14). Division of Agriculture Chemicals. New Delhi: Indian Agricultural Research Institute.

  5. Kumari, B., Madan, V. K., Kumar, R., & Kathpal, T. S. (2002). Monitoring of seasonal vegetables for pesticide residue. Environmental Monitoring and Assessment, 74, 263–270.

    Article  CAS  PubMed  Google Scholar 

  6. Kumari, B., Kumar, R., Madan, V. K., Singh, R., Singh, J., & Kathpal, T. S. (2003). Magnitude of pesticidal contamination in winter vegetables from Hisar, Hariana. Environmental Monitoring and Assessment, 87, 311–318.

    Article  CAS  PubMed  Google Scholar 

  7. Kumari, B., Madan, V. K., & Kathpal, T. S. (2006). Monitoring of pesticide residues in fruits. Environmental Monitoring and Assessment, 123, 407–412.

    Article  CAS  PubMed  Google Scholar 

  8. Hussain, S., Masud, T., & Ahad, K. (2002). Determination of pesticides residues in selected varieties of mango. Asian network for scientific information. Pakistan Journal of Nutrition, 1, 41–42.

    Article  Google Scholar 

  9. Fortin, M. C., Carrier, G., & Bouchard, M. (2008). Concentrations versus amounts of biomarkers in urine: A comparison of approaches to assess pyrethroid exposure. Environ Health, 7, 55–68.

    Article  PubMed  Google Scholar 

  10. Leng, G., Gries, W., & Selim, S. (2006). Biomarker of pyrethrum exposure. Toxicology Letters, 162, 195–201.

    Article  CAS  PubMed  Google Scholar 

  11. 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, 332, 71–80.

    Article  CAS  PubMed  Google Scholar 

  12. 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. The Journal of pharmacology and experimental therapeutics, 298, 1067–1082.

    CAS  PubMed  Google Scholar 

  13. Berlin, J. R., Akera, T., Brody, T. M., & Matsumara, F. (1984). Changes in neuromuscular transmission of guinea pig vas deferens produced by decamethrin treatment. European Journal of Pharmacology, 98, 313–322.

    Article  CAS  PubMed  Google Scholar 

  14. Luty, S., Latuszynska, J., Halliop, J., Tochman, A., Obuchowska, D., Przylepa, E., et al. (1998). Toxicity of dermally applied alpha-cypermethrin in rats. Annals of Agricultural and Environmental Medicine, 5, 109–116.

    CAS  PubMed  Google Scholar 

  15. Mueller, C. F., Laude, K., McNally, J. S., & Harrison, D. G. (2005). ATVB in focus: Redox mechanisms in blood vessels. Arteriosclerosis, Thrombosis, and Vascular Biology, 25, 274–278.

    Article  CAS  PubMed  Google Scholar 

  16. Van Gaal, L. F., Mertens, I. L., & De Block, C. E. (2006). Mechanisms linking obesity with cardiovascular disease. Nature, 444, 875–880.

    Article  PubMed  Google Scholar 

  17. Droge, W. (2002). Free radicals in the physiological control of cell function. Comprehensive overview of the reactions involved in generating and scavenging reactive oxygen radicals, good insight into antioxidant mechanisms of action. Physiological Reviews, 82, 47–95.

    CAS  PubMed  Google Scholar 

  18. You, H., Kim, G., Kim, Y., Chun, Y., Park, J., Chung, M. H., et al. (2000). Increased 8-hydroxyguanine formation and endonuclease activity for its repair in ischemic-reperfused hearts of rats. Journal of Molecular and Cellular Cardiology, 32, 1053–1059.

    Article  CAS  PubMed  Google Scholar 

  19. Golubnitschaja, O., Moenkemann, H., Kim, K., & Mozaffari, M. S. (2003). DNA damage and expression of checkpoint genes p21 (WAF1/CIP1) and 14–3-3 sigma in taurine-deficient cardiomyocytes. Biochemical Pharmacology, 66, 511–517.

    Article  CAS  PubMed  Google Scholar 

  20. Berwick, M., & Vineis, P. (2000). Markers of DNA repair and susceptibility to cancer in humans: An epidemiologic review. Journal of the National Cancer Institute, 92, 874–897.

    Article  CAS  PubMed  Google Scholar 

  21. Kastan, M. B., & Bartek, J. (2004). Cell-cycle checkpoints and cancer. Nature, 432, 316–323.

    Article  CAS  PubMed  Google Scholar 

  22. Singh, N. P., McCoy, M. T., Tice, R. R., & Schneider, E. L. (1988). A simple technique for quantification of low levels of DNA damage in individual cells. Experimental Cell Research, 175, 184–191.

    Article  CAS  PubMed  Google Scholar 

  23. Hellman, B., Brodin, D., Andersson, M., Dahlman-Wright, K., Isacsson, U., Brattstrom, D., et al. (2005). Radiation-induced DNA-damage and gene expression profiles in human lung cancer cell lines with different radiosensitivity. Experimental oncology, 27(2), 102–107.

    CAS  PubMed  Google Scholar 

  24. Report of FAO. Pesticide residues in food 1981, Monographs paper 42, Geneva, November–December 1981.

  25. Kakko, I., Toimela, T., & Tahti, H. (2003). The synaptosomal membrane bound ATPase as a target for the neurotoxic effects of pyrethroids, permethrin and cypermethrin. Chemosphere, 51, 475–480.

    Article  CAS  PubMed  Google Scholar 

  26. Grosman, N., & Diel, F. (2005). Influence of pyrethroids and piperonyl butoxide on the Ca (2+)-ATPase activity of rat brain synaptosomes and leukocyte membranes. International Immunopharmacology, 5, 263–270.

    Article  CAS  PubMed  Google Scholar 

  27. Gabbianelli, R., Falcioni, M. L., Cantalamessa, F., & Nasuti, C. (2009). Permethrin induces Endo III and Fpg lymphocyte DNA damage and change in monocyte respiratory burst in rats. Journal of Applied Toxicology, 29(4), 317–322.

    Article  CAS  PubMed  Google Scholar 

  28. Van der Wees, C. G., Vreeswijk, M. P., Persoon, M., Van der Laarse, A., Van Zeeland, A. A., & Mullenders, L. H. (2003). Deficient global genome repair of UV-induced cyclobutane pyrimidine dimers in terminally differentiated myocytes and proliferating fibroblasts from the rat heart. DNA Repair, 2, 1297–1308.

    Article  PubMed  Google Scholar 

  29. Pool-Zobel, B. L., Guigas, C., Klein, R. G., Neudecker, C. H., Renner, H. W., & Schnezer, P. (1993). Assessment of genotoxic effect by lindane. Food and Chemical Toxicology, 31, 271–283.

    Article  CAS  PubMed  Google Scholar 

  30. Moretti, M., Villarini, M., Scasselati-Sforzolini, G., Santoni, A. M., Fedeli, D., & Falcioni, G. (1998). Extent of DNA damage in density-separated trout erythrocytes assessed by “Comet” assay. Mutation Research, 397, 353–360.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  34. Parasassi, T., De Stasio, G., Ravagnan, G., Rusch, 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  CAS  PubMed  Google Scholar 

  35. Kumaravel, T. S., & Jha, A. N. (2006). Reliable comet assay measurements for detecting DNA damage induced by ionising radiation and chemicals. Mutation Research, 605, 7–16.

    CAS  PubMed  Google Scholar 

  36. Fairbain, D. W., Olive, P. L., & O’Neill, K. L. (1995). The comet assay: A comprehensive review. Mutation Research, 339, 37–59.

    Google Scholar 

  37. Tice, R. R., Agurell, E., Anderson, D., Burlinson, B., Hartmann, A., Kobayashi, H., et al. (2000). Single cell gel/comet assay: Guidelines for in vitro and in vivo genetic toxicology testing. Environmental and Molecular Mutagenesis, 35, 206–221.

    Article  CAS  PubMed  Google Scholar 

  38. Olive, P. L., Johnston, P. J., Banath, J. P., & Durand, R. E. (1998). The comet assay: A new method to examine heterogeneity associated with solid tumours. Nature Medicine, 4, 103–105.

    Article  CAS  PubMed  Google Scholar 

  39. Collins, A. R. (2004). The comet assay for DNA damage and repair. Molecular Biotechnology, 26, 249–261.

    Article  CAS  PubMed  Google Scholar 

  40. Nishi, E. E., Campos, R. R., Bergamaschi, C. T., De Almeida, V. R., & Ribeiro, D. A. (2010). Vitamin C prevents DNA damage induced by renovascular hypertension in multiple organs of Wistar rats. Human & Experimental Toxicology, 29(7), 593–599.

    Article  CAS  Google Scholar 

  41. Lenzi, P., Frenzilli, G., Gesi, M., Ferrucci, M., Lazzeri, G., Fornai, F., et al. (2003). DNA damage associated with ultrastructural alterations in rat myocardium after loud noise exposure. Environmental Health Perspectives, 111, 467–471.

    Article  CAS  PubMed  Google Scholar 

  42. Smith, C. C., O’Donovan, M. R., & Martin, E. A. (2006). HOGG1 recognizes oxidative damage using the comet assay with greater specificity than FPG or ENDOIII. Mutagenesis, 21, 185–190.

    Article  CAS  PubMed  Google Scholar 

  43. Halliwell, B., & Aruoma, O. I. (1991). DNA damage by oxygen-derived species. Its mechanism and measurement in mammalian systems. FEBS Letters, 281, 9–19.

    Article  CAS  PubMed  Google Scholar 

  44. Ferrari, R., Agnoletti, L., Comini, L., Gaia, G., Bachetti, T., Cargnoni, A., et al. (1998). Oxidative stress during myocardial ischemia and heart failure. European Heart Journal Supplements, B19, 2–11.

    Google Scholar 

  45. Tomascik-Cheeseman, L. M., Coleman, M. A., Marchetti, F., Nelson, D. O., Kegelmeyer, L. M., Nath, J., et al. (2004). Differential basal expression of genes associated with stress response, damage control, and DNA repair among mouse tissues. Mutation Research, 561, 1–14.

    CAS  PubMed  Google Scholar 

  46. Caroline, G. C., Van der Wees, P. G., Vreeswijk, M., Persoonmoud, A., Van der Laarse, A., Zeeland, H. F., et al. (2003). Deficient global genome repair of UV-induced cyclobutane pyrimidine dimers in terminally differentiated myocytes and proliferating fibroblasts from the rat heart. DNA Repair, 2, 1297–1308.

    Article  Google Scholar 

  47. Marguet, D., Lenne, P. F., Rigneault, H., & He, H. T. (2006). Dynamics in the plasma membrane: How to combine fluidity and order. The EMBO Journal, 25(15), 3446–3457.

    Article  CAS  PubMed  Google Scholar 

  48. Cester, N., Rabini, R. A., Salvolini, E., Staffolani, R., Curatola, A., Pugnaloni, A., et al. (1996). Activation of endothelial cells during insulin-dependent diabetes mellitus: A biochemical and morphological study. European Journal of Clinical Investigation, 26, 569–573.

    Article  CAS  PubMed  Google Scholar 

  49. Sojcic, Z., Toplak, H., Zuehlke, R., Honegger, U. E., Buhlmann, R., & Wiesmann, U. N. (1992). Cultured human skin fibroblasts modify their plasma membrane lipid composition and fluidity according to growth temperature suggesting homeoviscous adaptation at hypothermic (30°) but not at hyperthermic (40°) temperatures. Biochimica et Biophysica Acta, 1104, 31–37.

    Article  CAS  PubMed  Google Scholar 

  50. Ohyashiki, T., Karino, T., Suzuki, S., & Matsui, K. (1996). Effect of aluminum ion on Fe (21)-induced lipid peroxidation in phospholipid liposomes under acidic conditions. Journal of Biochemistry, 120, 895–900.

    CAS  PubMed  Google Scholar 

  51. Gabbianelli, R., Falcioni, M. L., Nasuti, C., Cantalamessa, F., Imada, I., & Inoue, M. (2009). Effect of permethrin insecticide on rat polymorphonuclear neutrophil. Chemico-Biological Interactions, 182(23), 245–252.

    Article  CAS  PubMed  Google Scholar 

  52. Kale, M. (1999). Lipid Peroxidation and Antioxidant Enzymes in Rat Tissues in Pyrethroid Toxicity: Possible Involvement of Reactive Oxygen Species. Journal of Nutritional & Environmental Medicine, 99, 37–46.

    Article  Google Scholar 

  53. Kale, M., Rathore, N., John, S., Bhatnagar, D., Nayyar, S. S., & Kothari, V. (1999). The protective effect of vitamin E in pyrethroid-induced oxidative stress in rat tissues. Journal of Nutritional and Environmental Medicine, 9, 281–287.

    Article  CAS  Google Scholar 

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Acknowledgments

This work was supported by FAR from UNICAM to R.G.

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Correspondence to Rosita Gabbianelli.

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Dhivya Vadhana, M.S., Nasuti, C. & Gabbianelli, R. Purine Bases Oxidation and Repair Following Permethrin Insecticide Treatment in Rat Heart Cells. Cardiovasc Toxicol 10, 199–207 (2010). https://doi.org/10.1007/s12012-010-9079-6

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