Experimental Study of Deltamethrin-Induced Nephrotoxicity in the Rat Model

ORIGINAL ARTICLE
Eugene A. Chigrinski, Taras V. Gerunov, Liudmila K. Gerunova, Yuri N. Fedorov, Nikolai V. Shorin

 
International Journal of Biomedicine. 2018;8(3):220-223.   
DOI: 10.21103/Article8(3)_OA10
Originally published September 15, 2018  

Abstract: 

The purpose of this study was to determine the nephrotoxic effect of deltamethrin in experimental animals at a dose of 43.5mg/kg (1/2 LD50).
Materials and Methods: For the experiment, 48 male Wistar rats with a body weight of 240±10g were divided into 4 groups of 12 animals each. Groups 1 and 3 were control groups, which were administered a physiological solution intragastrically. The animals in Groups 2 and 4 received a single dose (43.5mg/kg) of the synthetic pyrethroid deltamethrin, which corresponds to 1/2 LD50. Rats were withdrawn from the experiment in two stages: 1) rats in Groups 1 and 2 – one day after the deltamethrin administration; 2) rats in Groups 3 and 4 – 3 days after the deltamethrin administration. Biochemical and pathomorphological changes in the kidneys were evaluated. The evaluation criteria were the content of pyruvate, inorganic phosphate, and glutathione and the activity of glutathione peroxidase activity (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST) in the kidneys. Histological preparations of kidney tissue were studied.
Results: The single administration of a toxic dose of deltamethrin caused a decrease in body weight of rats, an increase in kidney weight, and the accumulation of pyruvate and inorganic phosphate in the kidneys. A decrease in the GSH content in the kidney was accompanied by an increase in the activity of GPx, GR and GST. One day after the experiment, in the convoluted tubules, epithelial cells with blurred contours of the boundaries were enlarged; and the granularity of the cytoplasm containing vacuoles was expressed. The nuclei of epithelial cells had different sizes; some of them were in a state of pycnosis.   In the organ parenchyma, large and small blood vessels full of blood were visible. Three days after the intoxication, these symptoms became more pronounced. In the intertubular connective tissue, hemorrhages and leukocyte infiltrates were detected.
Conclusion: The study confirms the nephrotoxic effect of a single toxic dose (43.5mg/kg [1/2LD50]) of deltamethrin. Pathomorphological changes in the kidneys are accompanied by the disturbances in energy metabolism and activation of the glutathione antioxidant system with the development of glutathione deficiency.

Keywords: 
pesticides • pyrethroids • deltamethrin • kidney • antioxidant system
References: 
  1. PubChem: Deltamethrin. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/deltamethrin#section=Top
  2. Katsuda Y. Progress and future of pyrethroids. Top Curr Chem. 2012;314:1-30. doi: 10.1007/128_2011_252. PubMed
  3. Kurek M, Barchańska H, Turek M. Degradation Processes of Pesticides Used in Potato Cultivations. Rev Environ Contam Toxicol. 2017;242:105-51. doi: 10.1007/398_2016_13. PubMed
  4. Bradberry SM, Cage SA, Proudfoot AT, Vale JA. Poisoning due to pyrethroids. Toxicol Rev. 2005;24(2):93-106. PubMed
  5. Vais H, Williamson MS, Devonshire AL, Usherwood PN. The molecular interactions of pyrethroid insecticides with insect and mammalian sodium channels. Pest Manag Sci. 2001;57(10):877-88. PubMed
  6. Shafer TJ, Meyer DA, Crofton KM. Developmental neurotoxicity of pyrethroid insecticides: critical review and future research needs. Environ Health Perspect. 2005. 113(2):123-36. PubMed
  7. Soderlund DM, Clark JM, Sheets LP, Mullin LS, Piccirillo VJ, Sargent D, et al. Mechanisms of pyrethroid neurotoxicity: implications for cumulative risk assessment. Toxicology. 2002;171(1):3-59. PubMed
  8. Taguchi S, Shimizu K, Yokote R, Uchiyama M, Sekii H, Kiyota K. [Three cases of inhalation of household pyrethroid and metoxadiazone insecticides with remarkable dyspnea]. Chudoku Kenkyu. 2006;19(2):147-53. [Article in Japanese]. PubMed
  9. Magdalan J, Zawadzki M, Merwid-Lad A. Fatal intoxication with hydrocarbons in deltamethrin preparation. Hum Exp Toxicol. 2009;28(12):791-3. doi: 10.1177/0960327109354939. PubMed
  10. Gunay N, Kekec Z, Cete Y, Eken C, Demiryurek AT. Oral deltamethrin ingestion due in a suicide attempt. Bratisl Lek Listy. 2010;111(5):303-5. PubMed
  11. Sharma P, Singh R, Jan M. Dose-dependent effect of deltamethrin in testis, liver, and kidney of wistar rats. Toxicol Int. 2014. 21(2):131-9. doi: 10.4103/0971-6580.139789. PubMed
  12. Nieradko-Iwanicka B, Borzecki A. How Deltamethrin Produces Oxidative Stress in Liver and Kidney. Pol J Environ Stud. 2016;25(3):1367-71. doi: 10.15244/pjoes/61818.
  13. Issam C, Samir H, Zohra H, Monia Z, Hassen BC. Toxic responses to deltamethrin (DM) low doses on gonads, sex hormones and lipoperoxidation in male rats following subcutaneous treatments. J Toxicol Sci. 2009;34(6):663-70. PubMed
  14. Khalatbary AR, Ghabaee DNZ, Ahmadvand H, Amiri FT, Lehi ST. Deltamethrin-Induced Hepatotoxicity and Virgin Olive Oil Consumption: An Experimental Study. Iran J Med Sci. 2017;42(6):586-592. PubMed
  15. Rousar T, Kucera O, Lotkova H, Cervinkova Z. Assessment of reduced glutathione: comparison of an optimized fluorometric assay with enzymatic recycling method. Anal Biochem. 2012;423(2):236-40. doi: 10.1016/j.ab.2012.01.030. PubMed
  16. Vlasova SN, Shabunina EI, Pereslegina IA. [The activity of the glutathione-dependent enzymes of erythrocytes in chronic liver diseases in children]. Lab Delo. 1990;8:19-22. [Article in Russian]. PubMed
  17. Habig WH, Jakoby WB. Glutathione S-transferases (rat and human). Methods Enzymol. 1981;77:218-31. PubMed
  18. Saoudi M, Badraoui R, Bouhajja H, Ncir M, Rahmouni F, Grati M, et al. Deltamethrin induced oxidative stress in kidney and brain of rats: Protective effect of Artemisia campestris essential oil. Biomed Pharmacother. 2017;94:955-63. doi: 10.1016/j.biopha.2017.08.030. PubMed
  19. Villarini M, Moretti M, Scassellati-Sforzolini G, Monarca S, Pasquini R, Crea MG et al. Studies on hepatic xenobiotic-metabolizing enzymes in rats treated with insecticide deltamethrin. J Environ Pathol Toxicol Oncol. 1995;14(1):45-52. PubMed
  20. Yousef MI, Awad TI, Mohamed EH. Deltamethrin-induced oxidative damage and biochemical alterations in rat and its attenuation by Vitamin E. Toxicology. 2006;227(3):240–7. PubMed
  21. Buhl MR. Purine metabolism in ischemic kidney tissue. Dan Med Bull. 1982;29(1):1-26. PubMed
  22. Lyakhovich VV, Vavilin VA, Zenkov NK, Menshchikova EB. Active defense under oxidative stress. The antioxidant responsive element. Biochemistry (Mosc). 2006;71(9):962-74. PubMed
  23. Li H, Wu S, Chen J, Wang B, Shi N. Effect of glutathione depletion on Nrf2/ARE activation by deltamethrin in PC12 Cells. Arh Hig Rada Toksikol. 2013;64(1):87-97. doi: 10.2478/10004-1254-64-2013-2251. PubMed
  24. Farber JL, Kyle ME, Coleman JB. Mechanisms of cell injury by activated oxygen species. Lab Invest. 1990;62(6):670-9. PubMed
  25. Sedor JR, Carey SW, Emancipator SN. Immune complexes bind to cultured rat glomerular mesangial cells to stimulate superoxide release. Evidence for an Fc receptor. J Immunol. 1987;138(11):3751-7. PubMed
  26. Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB. Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal. 2014;20(7):1126-67. doi: 10.1089/ars.2012.5149. PubMed
  27. Ratliff BB, Abdulmahdi W, Pawar R, Wolin MS. Oxidant Mechanisms in Renal Injury and Disease. Antioxid Redox Signal. 2016;25(3):119-46. doi: 10.1089/ars.2016.6665. PubMed

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Received August 15, 2018.
Accepted August 30, 2018.
©2018 International Medical Research and Development Corporation.