Rajinder RAINA, Naseer BABA, Pawan VERMA, Mudasir SULTANA

Free radical-induced nephrotoxicity following repeated oral exposureto chlorpyrifos alone and in conjunction with fluoride in rats

Background/aim: Chronic renal disorder is becoming a major health problem worldwide. The purpose of the present study was to investigate alterations in the renal antioxidant system in rats induced by repeated exposure to chlorpyrifos (CPF) alone and in conjunction with fluoride. Materials and methods: Wistar rats were randomly allocated to seven groups, each consisting of six rats, and were subjected to different treatment regiments for 28 days. Results: Significant increases (P < 0.05) in plasma protein, blood urea nitrogen, and creatinine levels indicated alterations in renal functions on repeated exposure to CPF or fluoride; moreover, these changes were more pronounced in animals exposed to both toxicants concurrently. A significant increase (P < 0.05) in malondialdehyde levels and decreases in superoxide dismutase, catalase, and glutathione peroxidase activities in renal tissue were noted, indicating renal damage on exposure to CPF, fluoride, or the combination of those. Conclusion: Our observations suggested that the concurrent exposure to CPF and fluoride increased the extent of renal damage. These findings indicate that this damage is due to increased free radical formation and a reduced function of the antioxidant system in renal tissue. Thus, the application of CPF as an insecticide should be reduced in areas where the fluoride levels in ground waters are high in order to minimize renal damage in exposed populations.

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1. Haroun MK, Jaar BG, Hoffman SC, Comstock GW, Klag MJ, Coresh J. Risk factors for chronic kidney disease: a prospective study of 23,534 men and women in Washington County, Maryland. J Am Soc Nephrol 2003; 14: 29342941.
2. Barsoum RS. Chronic kidney disease in the developing world. New Engl J Med 2006; 354: 997999.
3. Uchino S. The epidemiology of acute renal failure in the world. Curr Opin Crit Care 2006; 12: 538543.
4. Fatima S, Yusufi AN, Mahmood R. Effect of cisplatin on renal brush border membrane enzymes and phosphate transport. Hum Exp Toxicol 2004; 23: 547554.
5. Mahmood I, Waters DHA. Comparative study of uranyl nitrate and cisplatin-induced renal failure in rat. Eur J Drug Metab Ph 1994; 19: 327336.
6. Zhavoronkov AA, Strochkova LS. Fluorosis geographical pathology and some experimental findings. Fluoride 1981; 14: 183191.
7. Heikal TM, Ghanem HZ, Soliman MS. Protective effect of green tea extracts against dimethoate induced DNA damage and oxidant/antioxidant status in male rats. Biohealth Science Bulletin 2011; 3: 111.
8. Halliwell B, Gutteridge JMC. Free Radicals in Biology and Medicine. 3rd ed. Oxford, UK: Oxford University Press; 2002.
9. Ogutcu A, Suludere Z, Kalender Y. Dichlorvos-induced hepatotoxicity in rats and the protective effects of vitamins C and E. Environ Toxicol Phar 2008; 26: 355361.
10. Ahmed NS, Mohamed AS, Abdel-Wahhab MA. Chlorpyrifosinduced oxidative stress and histological changes in retinas and kidney in rats: protective role of ascorbic acid and alpha tocopherol. Pestic Biochem Phys 2010; 98: 3338.
11. Marklund S, Marklund G. Involvement of superoxide anion radical in autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 1974; 47: 469474.
12. Aebi HE. Catalase. In: Bergmeyer HU, editor. Methods of Enzymatic Analysis. Vol 3. New York, NY, USA: Academic Press; 1983. pp. 276286.
13. Hafeman DG, Sunde RA, Hoekstra WG. Effect of dietary selenium on erythrocyte and liver glutathione peroxidase in the rat. J Nutr 1974; 104: 580587.
14. Shafiq-ur-Rehman. Lead induced regional lipid peroxidation in brain. Toxicol Lett 1984; 21: 333337.
15. Duncan DB. Multiple range and multiple F tests. Biometrics 1955; 11: 142.
16. Hoitsma AJ, Wetzels JF, Koene RA. Drug induced nephrotoxicity. Etiology, clinical features and management. Drug Safety 1991; 6: 131147.
17. Oncu M, Gultekin F, Karaoz E, Altuntas I, Delibas N. Nephrotoxicity in rats induced by chlorpyrifos-ethyl and ameliorating effects of antioxidants. Hum Exp Toxicol 2002; 21: 223230.
18. Ambali SF, Abubakar AT, Shittu M, Yaqub LS, Anafi SB, Abdullahi A. Chlorpyrifos induced alteration of hematological parameters in Wistar rats: ameliorative effect of zinc. Research Journal of Environmental Toxicology 2010; 4: 5566.
19. Kant V, Srivastava AK, Verma PK, Raina R. Alterations in the biochemical parameters during sub-acute toxicity of fluoride alone and in conjunction with aluminum sulphate in goats. Biol Trace Elem Res 2009; 130: 2030.
20. Mansoor SA, Mossa AH. Lipid peroxidation and oxidative stress in rat erythrocytes induced by chlorpyrifos and protective role of zinc. Pestic Biochem Phys 2009; 93: 3439.
21. Verma RS, Mnugya A, Srivastava N. Effect of chlorpyrifos on lipid peroxidation, scavenging enzymes and glutathione in rat tissues. Pestic Biochem Phys 2003; 54: 149156.
22. Hayes JD, Paiford DJ. The glutathione-S-transferase supergene family. Regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol 1995; 30: 445600.
23. Shivarajashankara YM, Shivashankara AR, Rao SH, Bhat PG. Oxidative stress in children with endemic skeletal fluorosis. Fluoride 2001; 34: 103107.
24. Tao X, Xu ZR, Wang YZ. Effects of dietary fluoride on growth, serum indexes and antioxidant systems in growing pigs. Turk J Vet Anim Sci 2006; 30: 6570.
25. Zhan X, Xu Z, Li J, Wang HM. Effects of fluorosis on lipid peroxidation and antioxidant systems in young pigs. Fluoride 2005; 38: 15761.
26. Rehman H, Ali M, Atif F, Kaur M, Bhatia K, Raisuddin S. The modulatory effect of deltamethrin on antioxidants in mice. Clin Chim Acta 2006; 369: 6165.
27. Shanthakumari D, Srinivasalu S, Subramanian S. Effect of fluoride intoxication on lipid peroxidation and antioxidant status in experimental rats. Toxicology 2004; 204: 219228.
28. Brigelius-Flohe R. Tissue-specific functions of individual glutathione peroxidases. Free Radical Bio Med 1999; 27: 951 965.
29.Fujii T, Endo T, Fujii J, Taniguchi N. Differential expression of glutathione reductase and cytosolic glutathione peroxidase, GPX1, in developing rat lungs and kidneys. Free Radical Res 2002; 36: 10411049.
30. Kayanoki Y, Fujii J, Islam KN, Suzuki K, Kawata S, Matsuzawa Y. The protective role of glutathione peroxidase in apoptosis induced by reactive oxygen species. J Biochem 1996; 119: 817 822.
31. Welch WS. How cells respond to stress. Sci Am 1993; 268: 34 41.
32. Inkielewicz I, Krechniak J. Fluoride effects on glutathione peroxidase and lipid peroxidation in rats. Fluoride 2004; 37: 712.
33. Xing H, Li S, Wang X, Gao X, Xu S, Wang X. Effects of atrazine and chlorpyrifos on the mRNA levels of HSP70 and HSC70 in the liver, brain, kidney and gill of common carp (Cyprinus carpio L.). Chemosphere 2013; 90: 8871316.
34. Yu F, Wang Z, Ju B, Wang Y, Wang J, Bai D. Apoptotic effect of organophosphorus insecticide chlorpyrifos on mouse retina in vivo via oxidative stress and protection of combination of vitamin C and E. Exp Toxicol Pathol 2008; 59: 415423.
35. Uzun FG, Kalender Y. Chloropyrifos-induced hepatotoxicity and hematologic changes in rats: the role of quercetin and catechin. Food Chem Toxicol 2013; 55: 549556.
36. Raina R, Verma PK, Pankaj NK, Kant V. Ameliorative effects of alpha-tocopherol on cypermethrin induced oxidative stress and lipid peroxidation in Wistar rats. International Journal of Medicine and Medical Sciences 2009; 1: 396399.
37. Raina R, Verma PK, Pankaj NK, Kant V, Prawez S. Protective effect of ascorbic acid on oxidative stress induced by repeated dermal application of cypermethrin. Toxicol Environ Chem 2010; 92: 947953.
38. Kalender Y, Kaya S, Durak D, Uzun FG, Demir F. Protective effects of catechin and quercetin on antioxidant status, lipid peroxidation and testis-histoarchitecture induced by chlorpyrifos in male rats. Environ Toxicol Phar 2012; 33: 141 148.
39. Demir F, Uzun FG, Durak D, Kalender Y. Subacute chlorpyrifosinduced oxidative stress in rat erythrocytes and the protective effects of catechin and quercetin. Pestic Biochem Phys 2011; 99: 7781.