Nephrotoxicity in rats induced by chlorpryfos-ethyl and ameliorating effects of antioxidantsy

Abstract

Nephrotoxicity induced by chlorpyrifos-ethyl (CE) and ameliorating effects of melatonin and vitamin E plus vitamin C were evaluated in rats exposed to CE. Experimental groups were as follows: control (C), CE treated (CE), vitamin E plus vitamin C treated (Vit), melatonin treated (Mel), vitamin E plus vitamin C plus CE treated (Vit+CE), and melatonin plus CE treated (Mel+CE). The rats in the CE, Vit+CE and Mel+CE groups were administered orally with CE in two equal doses of 41 mg/kg body weight (0.25 LD₅₀). Melatonin and vitamins E and C were administrated intramuscularly at the doses of 10, 150 and 200 mg/kg, respectively. The levels of thiobarbituric acid reactive substance (TBARS) and antioxidant potential (AOP), and the activities of glutathione peroxidase (GSHPx), catalase (CAT) and superoxide dismutase (SOD) were studied in the homogenates of kidney tissue. There were no significant differences in the activities of SOD and CAT between the experimental groups. The level of TBARS increased significantly (P<0.05) while AOP decreased significantly (P<0.05) in the CE group compared with the C group. GSH-Px activity was significantly (P<0.05) lower in the CE group and higher in the melatonin group than the control group. Histopathological changes were found in the kidney tissue of rats treated with CE. These were infiltration in mononuclear cells at perivascular and peritubular areas, hydropic degenerations in tubule epithelium and glomerular sclerosis. The severity of the lesions was reduced by administration of vitamins and melatonin. These results suggest that CE increases lipid peroxidation and decreases AOP by increasing oxidative stress, and that high doses of melatonin and a combination of vitamin E plus vitamin C considerably reduce the toxic effect of CE on kidney tissue of rats.

Keywords

antioxidant enzymes kidney lipid peroxidation melatonin vitamin C vitamin E

References

Richardson RJ . Assessment of the neurotoxic potential of chlorpyrifos relative to other organophosphorus compounds: a critical review of the literature . J Toxicol Environ Health 1995; 44: 135–165 .

Chambers JE , Ma T , Boone JS , Chambers HW . Role of detoxication pathways in acute toxicity levels of phosphorothionate insecticides in the rat . Life Sci 1994; 54: 1357–1364 .

Atterbery TT , Burnett WT , Chambers JE . Age-related differences in parathion and chlorpyrifos toxicity in male rats: target and non-target esterase sensitivity and cytochrome p450-mediated metabolism . Toxicol Appl Pharmacol 1997; 147: 411–418 .

Lawrence LJ , Casida JE . Interactions of lindane, toxaphene and cyclodiene with brain-specific t-butylbicyclophorothianate receptor . Life Sci 1984; 35: 171–178 .

Song X , Seidler FJ , Saleh JL , Zhang J , Padilla S , Slotkin TA . Cellular mechanisms for developmental toxicity of chlorpyrifos: targeting the adenylyl cyclase signaling cascade . Toxicol Appl Pharmacol 1997; 145: 158–174 .

Lodovici M , Aiolli S , Monserrat C , Dolara P , Medica A , Di Simplicio P. Effect of a mixture of 15 commonly used pesticides on DNA levels of 8-hydroxy-2-deoxyguanosine and xenobiotic metabolising enzymes in rat liver . J Environ Pathol Toxicol Oncol 1994; 13: 163–168 .

Bagchi D , Bagchi M , Hassoun EA , Stohs SJ . In vitro and in vivo generation of reactive oxygen species, DNA damage and lactate dehydrogenase leakage by selected pesticides . Toxicology 1995; 104: 129–140 .

Datta C , Gupta J , Sarkar A , Sengupta D. Effects of organophosphorus insecticide phosphomidon on antioxidant defence components of human erythrocyte and plasma . Indian J Exp Biol 1992; 30: 65–67 .

Dwivedi PD , Das M , Khanna SK . Role of cytochrome p-450 in quinalphos toxicity: effect on hepatic and brain antioxidant enzymes in rats . Food Chem Toxicol 1998; 36: 437–444 .

10.

Gultekin F , Delibas N , Arican A , Sutcu R , Kilinc I , Kaptanagasi M. Investigation of the relation between LD50 and lipoperoxidative effect of certain agrochemical . Biomedical Research 2000; 11: 67–71 .

11.

Gultekin F , Ozturk M , Akdogan M. The effect of organophosphate insecticide chlorpyrifos-ethyl on lipid peroxidation and antioxidant enzymes (in vitro) . Arch Toxicol 2000; 74: 533–538 .

12.

Gultekin F , Delibas N , Yasar S , Kilinc I. In vivo changes in antioxidant systems and protective role of melatonin and a combination of vitamin C and vitamin E on oxidative damage in erythrocytes induced by chlorpyrifos-ethyl in rats . Arch Toxicol 2001; 75: 88–96 .

13.

Gultekin F , Kaleli S , Altuntas I , Oncu M , Gokcimen A , Sutcu R. The in vivo lipoperoxida tive effect of chlorpyrifos-ethyl on testis tissue of rats . Gen Tip Derg 2000; 10: 147–152 .

14.

Gultekin F , Delibas N , Kutluhan S , Akdogan M , Kilinc I , Sutcu R. The changes in antioxidant system caused by chlorpyrifos-ethyl in rat brain and protective effect of melatonin and vitamin C+vitamin E . Selçuk Üniv tip Fak Derg 2001; 17: 79–86 .

15.

Aslan R , Sekeroglu MR , Gultekin F , Bayiroglu F. Blood lipoperoxidation and antioxidant enzymes in healthy individuals: relation to age, sex, habits, life style and environment . J Environ Sci Health 1997; A32: 2101–2109 .

16.

Draper HH , Hadley M. Malondialdehyde determination as index of lipid peroxidation . Methods Enzymol 1990; 186: 421–431 .

17.

Gallo MA , Lawryk NJ . Organic phosphorus pesticides. In Hayes WJ , Laws ER eds. Handbook of pesticide toxicology. New York, NY: Academic Press , 1991. http://ace.orst.edu/cgi-bin/mfs/01/pips/chlorpyr.htm?6%23mfs

18.

Kidd H , James DR eds. The agrochemicals handbook, third edition. Cambridge, UK: Royal Society of Chemistry Information Services , 1991.

19.

Gosselin RE , Smith RP , Hodge HC . Clinical toxicology of commercial products, fifth edition. Baltimore, MD: Williams & Wilkins , 1984.

20.

Lu FC . A review of the acceptable daily intakes of pesticides assessed by the World Health Organization . Regul Toxicol Pharmacol 1995; 21: 351–364 .

21.

Kidd H , James DR . The agrochemicals handbook, third edition. Cambridge: Royal Society of Chemistry Information Services , 1991.

22.

Hazardous Substance Data Bank. U.S. Public Health Service. Washington, DC, 1995.

23.

Lisoni P , Resentini M , Mauri R , et al. Effect of an acute injection of melatonin on the basal secretion of hypophyseal hormones in prepubertal and pubertal healthy subjects . Acta Endocrinol 1986; 111: 305–311 .

24.

Lu J , Zoran MJ , Cassone VM . Daily and circadian variation in the electroretinogram of the domestic fowl: effects of melatonin . J Comp Physiol [A] 1995; 177: 299–306 .

25.

Black WD , Hidiroglou M. Pharmacokinetic study of ascorbic acid in sheep . Can J Vet Res 1996; 60: 216–221 .

26.

Kennes B , Dumont I , Brohee D , Hubert C , Neve P. Effect of vitamin C supplements on cell-mediated immunity in old people . Gerontology 1983; 29: 305–310 .

27.

Augustin AJ , Breipohl W , Boker T , Wegener A. Evidence for the prevention of oxidative tissue damage in the inner eye by vitamins E and C . Ger J Ophthalmol 1992; 1: 394–398 .

28.

Lowry OH , Rosebrough NJ , Farr WL , Randall RJ . Protein measurement with the folin phenol reagent . J Biol Chem 1951; 193: 265–272 .

29.

Durak I , Karabacak HI , Buyukkocak S , et al. Impaired antioxidant defense system in the kidney tissues from rabbits treated with cyclosporine. Protective effects of vitamins E and C . Nephron 1998; 78: 207–211 .

30.

Paglia DE , Valentine WN . Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase . J Lab Clin Med 1967; 70: 158–169 .

31.

Woolliams JA , Wiener G , Anderson PH , McMurray CH . Variation in the activities of glutathione peroxidase and superoxide dismutase and in the concentration of copper in the blood in various breed crosses of sheep . Res Vet Sci 1983; 34: 253–256 .

32.

Aebi H. Catalase in vitro . Methods Enzymol 1984; 105: 121–126 .

33.

Kiernan AJ . Histological and histochemical methods. Theory and practice. Oxford: Pergamon Press , 1990.

34.

Dawson-Saunders B , Trapp RG . Basic and clinical statistics. Norwalk CT: Appleton & Lange , 1994.

35.

Blum J , Fridovich I. Inactivation of glutathione peroxidase by superoxide radical . Arch Biochem Biophys 1985; 240: 500–508 .

36.

Kono Y , Fridovich I. Superoxide radical inhibits catalase . J Biol Chem 1982; 257: 5751–5754 .

37.

Escobar JA , Rubio MA , Lissi EA . SOD and catalase inactivation by singlet oxygen and peroxyl radicals . Free Radic Biol Med 1996; 20: 285–290 .

38.

Reiter RJ . Functional aspects of the pineal hormone melatonin in combating cell and tissue damage induced by free radicals . Eur J Endocrinol 1996; 134: 412–420 .

39.

Daniels WM , Reiter RJ , Melchiorri D , Severynek E , Pablos MI , Ortiz GG . Melatonin counteracts lipid peroxidation induced by carbon tetrachloride but does not restore glucose-6-phosphatase activity . J Pineal Res 1995; 19: 1–6 .

40.

Gurbilek M , Vatansev H , Gultekin F , Dilsiz A , Vatansev C. Prevention of testicular damage by free radical scavengers after acute experimental torsion . Biomed Res 2000; 11: 315–319 .

41.

Barlow-Walden LR , Reiter RJ , Abe M , et al. Melatonin stimulates brain glutathione peroxidase activity . Neurochem Int 1995; 26: 497–502 .

42.

Antolin I , Rodriguez C , Sainz RM , et al. Neurohormone melatonin prevents cell damage: effect on gene expression for antioxidant enzymes . FASEB J 1996; 10: 882–890 .