03May 2019


  • Department of Pathology, Faculty of Veterinary Medicine, University of Sadat City, Egypt.
  • Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, University of Sadat City.
  • Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt.
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Bifenthrinis a third-generation synthetic pyrethroid with a broad spectrum insecticidal and acaricidal activity used to control a wide range of insect pests in many applications. The current study was designed to investigate the toxic effects of bifenthrin in male rats exposed orally by stomach intubation at 7 mg/kg for 28 days. Liver and kidney functions were monitored in addition to oxidant/antioxidant parameters inserum, liver, kidney and brain. The immunohistochemical reactivity to iNOS, COX-2 and caspase-3 were studied and the histopathological findings were recorded. Our results revealed significant elevations in serum ALT, AST, LDH and ALP activities and blood BUN and creatinine levels while serum total protein was reduced. The level of MDA increased in liver, kidney and brain with reduction in GSH level and SOD, CAT and GPx activities. The activity of iNOS increased in hepatocytes, glomeruli and renal tubular cells. Strong immunoreactivity to COX-2 was observed in the brain. The expression of caspase-3 increased in both liver and brain. The liver revealed degeneration with loss of cellular outlines and areas of coagulative necrosis infiltrated with inflammatory cells. The kidney showed congestion of blood vessels and glomeruli, necrotic renal tubules and hyperplasia of fibrocytes with leucocyte infiltration in-between renal tubules. The brain revealed loss of some Purkinje cells, demyelination, neuronophagia, widespread neuronal necrosis with marked edema and proliferation of perineural satellite oligodendroglia cells around the cell body of motor neurons ?satellitosis?. In conlusion, bifenthrin produced toxic effects in rats which seem to be mediated by oxidative stress and release of inflammatory mediators.

  1. Aebi, H. (1984): Catalase in vitro. Methods Enzymol., 105: 121?126.
  2. Anad?n, A., Mart?nez-Larra?aga, M. and Mart?nez, M.A. (2009): Use and abuse of pyrethrins and synthetic pyrethroids in veterinary medicine. Vet .J. Lond. Engl., 182: 7?20.
  3. Aouey, B., Derbali, M., Chtourou, Bouchard, M., Khabir, A. and Fetoui, H. (2017): Pyrethroid insecticide lambda-cyhalothrin and its metabolites induce liver injury through the activation of oxidative stress and proinflammatory gene expression in rats following acute and subchronic exposure. Environ. Sci. Pollut. Res. Int., 24: 5841?5856.
  4. Bagchi, D., Bagchi, M., Hassoun, E.A. and Stohs, S.J. (1995): In vitro and in vivo generation of reactive oxygen species, DNA damage and lactate dehydrogenase leakage by selected pesticides. Toxicol., 104: 129?
  5. Bais, R. and Philcox, M. (1994): Approved recommendation on IFCC methods for the measurement of catalytic concentration of enzymes. Part 8. IFCC method for LDH. Eur. J. Clin. Chem. Clin. Biochem., 32: 639-55.
  6. Bancroft, J.D. and Gamble, M. (2008): Theory and Practice of histological techniques\". 6th Edition. Churchill, Livingstone, New York, London.,Pp: 440-450.
  7. Beutler, E., Duron, O.B.M. and Kelly, B.M. (1963): Improved method for the determination of blood glutathione, J. Lab. Clin. Med., 61: 882?888.
  8. Choi, S.H., Aid, S., Caracciolo, L., Minami, S.S., Niikura, T., Matsuoka, Y., Turner, R.S., Mattson, M.P. and Bosetti, F. (2013). Cyclooxygenase-1 inhibition reduces amyloid pathology and improves memory deficits in a mouse model of Alzheimer\'s disease. J. Neurochem.,124: 59?68.
  9. Dar, M.A., Khan, A.M., Raina, R., Verma, P.K. and Sultana, M. (2013): Effect of repeated oral administration of bifenthrin on lipid peroxidation and antioxidant parameters in Wistar rats. Bull. Environ. Contam. Toxicol., 91(1): 125-8.
  10. Dar, M.A., Raina, R., Mir, A.H., Sultana, M. and Pankaj, N.K. (2015): Effect of Dermal Application of Bifenthrin on Acetylcholinesterase and Oxidative Stress Induced in Rat Blood, Lung and Kidney. Proc. Natl. Acad. Sci., India, Sect. B. Biol. Sci., 85(2): 431?435
  11. de Oliveira, A.C.P, Yousif, N.M., Bhatia, H.S., Hermanek, J., Huell, M. and Fiebich, B.L. (2016). Poly(I:C) increases the expression of mPGES-1 and COX-2 in rat primary microglia. J. Neuroinflamm., 13: 11.
  12. El-Aaser, A.A., Hindawy, D.S., Hammouda, F. and Mohieddin, O. (1977): A direct lead technique for histochemical demonstration of leucocyte alkaline phosphatase activity in blood smears. Acta Biol. Acad. Sci. Hung, 28(3): 291-8.
  13. Fawcett, J.K. and Scott, J.E. (1960). A rapid and precise method for the determination of urea. J. Clin. Pathol., 13: 156-159.
  14. Gargouri, B., Bhatia, H.S., Bouchard, M., Fiebich, B.L. and Fetoui, H. (2018a). Inflammatory and oxidative mechanisms potentiate bifenthrin-induced neurological alterations and anxiety-like behavior in adult rats. Toxicol. Lett., 294: 73-86.
  15. Gargouri, B., Yousif, N.M., Attaai, A., Bouchard, M., Chtourou, Y., Fiebich, B.L. and Fetoui, H. (2018c): Pyrethroidbifenthrin induces oxidative stress, neuroinflammation, and neuronal damage, associated with cognitive and memory impairment in murine hippocampus. Neurochem. Int., 120: 121-133.
  16. Gargouri, B., Yousif, N.M., Bouchard, M., Fetoui, H. and Fiebich, B.L. (2018b): Inflammatory and cytotoxic effects of bifenthrin in primary microglia and organotypic hippocampal slice cultures. J. Neuroinflamm., 15(1): 159.
  17. Gornall, A.G. Bradawill, C.J. and David, M.M. (1949): Determination of serum proteins by means of the biuret reaction. J. Biol. Chem., 177(2): 751-66.
  18. G?nd?z, E., ?lger, B.V., İbiloğlu, İ., Ekinci, A., Dursun, R., Zengin, Y., İ?er, M., Uslukaya, ?.,Ekinci, C. and G?loğlu, C. (2015): Glutamine provides effective protection against deltamethrin-induced acute hepatotoxicity in rats but not against nephrotoxicity. Sci. Monit., 21:1107-14.
  19. Hall, R.L. and Everds, N.E. (2014): Principles of clinical pathology for toxicology studies. In: \"Hayes\' Principles and Methods of Toxicology\". 6th ed. By: AW Hayes and CL Kruger. CRC Press, New York.,Pp. 1305-1344.
  20. Hocine, L., Merzouk, H., Merzouk, S.A., Ghorzi,, H., Youbi, M. and Narce, M. (2016): The effects of alpha-cypermethrin exposure on biochemical and redox parameters in pregnant rats and their newborns. Biochem. Physiol., 134: 49-54.
  21. Iwakiri, Y. and Kim, Y. (2015):Nitric oxide in liver diseases.Trends. Pharmacol. Sci., 36(8): 524-36.
  22. Johnson, M., Luukinen, B., Gervais, J., Buhl, K. and Stone, D. (2010): Bifenthrin Technical Fact Sheet; National Pesticide Information Center, Oregon State University Extension Services. http://npic.orst.edu/factsheets/archive/biftech.html.
  23. Kale, M., Rathore, N., John, S. and Bhatnagar, D. (1999): Lipid peroxidative damage on pyrethroid exposure and alterations in antioxidant status in rat erythrocyte: a possible involvement of reactive oxygen species. Toxicol. Lett., 105: 197?205.
  24. Khan, A.M, Sultana, M., Raina, R., Dubey, N. and Dar, S.A. (2013): Effect of sub-acute toxicity of bifenthrin on antioxidant status and hematology after its oral exposure in goats. Proc. Natl. Acad. Sci., India, Sect. B Biol. Sci., 83(4): 545?549.
  25. Koracevic, D., Koracevic, G., Djordjevic, V., Andrejevic, S. and Cosic, V. (2001): Method for the measurement of antioxidant activity in human fluids. J. Clin. Pathol., 54: 361-356.
  26. Mart?nez, M.A., Ares, I., Rodr?guez, J.L., Mart?nez, M., Roura-Mart?nez, D., Castellano, V., Lopez-Torres, B., Mart?nez-Larra?aga, M.R. and Anad?n, A. (2018): Pyrethroid insecticide lambda-cyhalothrin induces hepatic cytochrome P450 enzymes, oxidative stress and apoptosis in rats. Sci. Total Environ., 631-632: 1371-1382.
  27. Nieradko-Iwanicka, B., Borzecki, A. and Jodlowska-Jedrych, B. (2015). Effect of subacute poisoning with bifenthrin on locomotor activity, memory retention, haematological, biochemical and histopathological parameters in mice. Physiol. Pharmacol., 66(1): 129-37.
  28. Nishikimi, M., Appaji, N. and Yagi, K. (1972): The occurrence of superoxide anion in the reaction of reduced phenazinemethosulfate and molecular oxygen, Biochem. Biophys. Res. Commun., 46: 849?854.
  29. Niu, H., ?lvarez-?lvarez, I., Guill?n-Grima, F. and Aguinaga-Ontoso, I. (2017): Prevalence and incidence of Alzheimer\'s disease in Europe: a meta-analysis. Neurologia, 32: 523?532.
  30. Nordberg, J. and Arn?r, E.S. (2001): Reactive oxygen species, antioxidants and the mammalian thioredoxin system. Free Radic. Biol. Med., 31: 1287-1317.
  31. Ohkawa, H., Ohishi, W. and Yagi, K. (1979): Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction, Anal. Biochem., 95: 351?358.
  32. Paglia, D.E. and Valentine, W.N. (1967):Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J. Lab. Clin. Med., 70(1):158-69.
  33. Plaa, G.L., Charbonneau, M. and Plante, I. (2014): Detection and evaluation of chemically induced liver injury. In: \"Hayes\' Principles and Methods of Toxicology\". 6th ed. By: A.W. Hayes and C.L. Kruger. CRC Press, New York. Pp:1384-1445.
  34. Prasanthi, K., Muralidharan, and Rajini, PS. (2005): Fenvalerate induced oxidative damage in rat tissue and its attenuation by dietary sesame oil. Food Chem. Toxicol., 43: 299?306.
  35. Raina, R., Verma, P.K., Pankaj, N.K. and Kant, V. (2009): Ameliorative effects of alfa-tocopherol on cypermethrin induced oxidative stress and lipid peroxidation in Wistar rats. Int. J. Med. Med. Sci., 1:396?399.
  36. Reitman, S. and Frankel, S. (1957): Colorimetric determination of serum oxalacetic and glutamic pyruvic transaminase. Amer. J. Clin. Pathol., 28: 56-63.
  37. Rjeibi, I., Ben Saad, A. and Hfaiedh, N. (2016): Oxidative damage and hepatotoxicity associated with deltamethrin in rats: The protective effects of Amaranthusspinosus seed extract. Pharmacother., 84: 853-860.
  38. Sankar P., Telang A.G. and Manimaran A. (2012): Protective effect of curcumin on cypermethrin-induced oxidative stress in Wistar rats. Toxicol. Pathol., 64(5): 487-93.
  39. Saoudi, M., Badraoui, R., Bouhajja, H., Ncir, M., Rahmouni, F., Grati, M., Jamoussi, K. and Feki, A.E. (2017): Deltamethrin induced oxidative stress in kidney and brain of rats: Protective effect of Artemisia campestris essential oil. Pharmacother., 94: 955-963.
  40. Schirmeister, J., Willmann, H. and Kiefer, H. (1964): Plasma creatinine as rough indicator of renal function. Dtsch. Med. Wochenschr., 89: 1018-23.
  41. Shupp, J.W., Nasabzadeh, T.J., Rosenthal, D.S., Jordan, M.H., Fidler, P. and Jeng, J.C. (2010): A review of the local pathophysiologic bases of burn wound progression. Burn. Care Res., 31: 849?873.
  42. Soliman, M.M., Attia, H.F. and El-Ella, G.A. (2015): Genetic and histopathological alterations induced by cypermethrin in rat kidney and liver: Protection by sesame oil. J. Immunopathol. Pharmacol., 28(4): 508-20.
  43. Sunderland, M. (2010): Toxicology and Mode of Action of Pyrethroid Insecticides. In: Handbook of Pesticide Toxicology. 3rd ed., R. Krieger, Academic Press, New York. Pp. 1665-86.
  44. Syed, F., John, P.J and Soni, I. (2016):Neurodevelopmental consequences of gestational and lactational exposure to pyrethroids in rats.Environ. Toxicol., 31(12): 1761-1770.
  45. Tsuji, R., Yamada, T. and Kawamura, S. (2012): Mammal Toxicology of Synthetic Pyrethroids. Top. Curr .Chem., 314: 83?112
  46. Velisek, J., Svobodova, Z. and Piackova, V. (2009): Effects of acute exposure to bifenthrin on some haematological, biochemical and histopathological parameters of rainbow trout (Oncorhynchusmykiss). Med., 54(3): 131?137.
  47. Wang, X., Mart?nez, M.A., Dai, M., Chen, D., Ares, I., Romero, A., Castellano, V., Mart?nez, M., Rodr?guez, J.L., Mart?nez-Larra?aga, M.R., Anad?n, A. and Yuan, Z. (2016). Permethrin-induced oxidative stress and toxicity and metabolism. A review. Environ. Res., 149: 86?104.
  48. Whalan, J.E. (2015): Clinical Chemistry. In: A Toxicologist?s Guide to Clinical Pathology in Animals. Springer International Publishing, Switzerland. Pp: 67-94.
  49. Yang, Y., Wu, N. and Wang, C. (2018): Toxicity of the pyrethroidbifenthrin insecticide. Environ. Chem. Lett., 16: 1377?1391.
  50. Zhang, Y., Lu, M, Zhou, P., Wang, C., Zhang, Q. and Zhao, M. (2015): Multilevel evaluations of potential liver injury of bifenthrin. Pestic. Biochem. Physiol., 122: 29-37.
  51. Zhang, Z., Zhao, X. and Qin, X. (2017): Potential genotoxic and cytotoxicity of emamectin benzoate in human normal liver cells. Oncotarget., 8: 82185?82195.

[Enas A. Tahoun, Shimaa M. Abou-Zeid and Huda O. AbuBakr. (2019); BIFENTHRIN INDUCED BIOCHEMICAL AND HISTOPATHOLOGICAL ALTERATIONS IN RATS. Int. J. of Adv. Res. 7 (5). 70-85] (ISSN 2320-5407). www.journalijar.com

Enas A. Tahoun
Department of Pathology, Faculty of Veterinary Medicine, University of Sadat City


Article DOI: 10.21474/IJAR01/9006       DOI URL: http://dx.doi.org/10.21474/IJAR01/9006

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