Chlorpyrifos-induced testicular damage in rats: The effect of glutathione antioxidant
Keywords:Chlorpyriphos, Testosterone, Alkaline phosphatase, Oxidative stress, Spermatogenesis
This study investigated the induction of oxidative stress in the testis of adult rat exposed to Chlorpyriphos (CPF). CPF was administered orally, in a dose of 30 mg/kg body weight to male rats for 90 days/ twice/ weekly. Co- administration of water soluble non enzymatic antioxidant glutathione (GSH) was given in a dose of 100 mg/kg body weight, oral, for the same period. Another two groups of male rats were administered GSH and corn oil, respectively. The activities of superoxide dismutase and glutathione reductase were decreased while the levels of lipid peroxidation were increased in the testicular tissues of the exposed animals. Testosterone hormone level in the serum was significantly decreased. The decrease in the histochemical determination of testicular alkaline phosphatase was observed in CPF-treated rats. A significant decrease in all stages of spermatogenesis in the seminiferous tubules was recorded in the exposed animals. Co-dministration of GSH restored these parameters.
Aitken, J.R., Clarkson, J.S., 1987. Cellular basis of defective sperm function and its association with the genesis of
reactive oxygen species by human spermatozoa. J Reprod Fertil. 81, 459–69.
Aitken, J.R., Clarkson, J.S., Fishel, S., 1989. Generation of reactive oxygen species, lipid peroxidation and humal
sperm function. Biol. Reprod. 40, 183–97.
Bagchi D, Balmoori J, Bagchi M, Ye X, Williams CB, Stohs SJ. 2002. Comparative effects of TCDD, endrin,
naphthalene and chromium (IV) on oxidative stress and tissue damage in the liver and brain tissues of mice.
Bairy, K.L., (2006). Neonatal methyl parathion exposure aVects the growth and functions of the male reproductive
system in the adult rat. Folia. Morphol. (Warsz) 65, 26–33
Banerjee, B.D., Seth, V., Bhattacharya, A., Pasha, S.T., Chakraborty, A.K., 1999. Biochemical effect of some
pesticides on lipid peroxidation and free radical scavengers, Toxicol. Lett. 107, 33–37.
Buege, J.A., Aust S.D., 1978 .Microsomal lipid peroxidation, Methods Enzymol. 52, 302–310.
Carlberg, I., Mannervik, B., 1975. Purification and characterization of the flavoenzyme glutathione reductase from
rat liver. J. Biol. Chem. 250, 5474–5480.
Chitra, K.C., Sujatha, R., Latchoumycandane, C., Mathur, P.P., 2001. Effect of lindane on antioxidant enzymes in
epididymis and epididymal sperm of adult rats. Asian. J. Androl.; 3, 205–8.
Debnath, D., Mandal, T.K., 2000. Study of quinalphos (an environmental oestrogenic insecticide) formulation
(Ekalux 25 E.C.)-induced damage of the testicular tissues and antioxidant defence systems in Sprague–Dawley
albino rats. J. Appl. Toxicol. 20,197–204.
Farag, A.T., El-Okazy, A.M., El-Aswed, A.F., 2003. Developmental toxicity study of chlorpyrifos in rats. Reprod.
Toxicol. 17, 203–8.
Farag, A.T., Radwana, H.A., Sorourb,F., El Okazyc, A., El-Agamyd, E., El-Sebaea, A., (2010). Chlorpyrifos induced
reproductive toxicity in male mice. Reprod. Toxicol. 29, 80–85.
Franca, L.R., Hass, R.A., Cooke, P.S. and Russell, L.D., 1995. Neonatal hypothyroidism causes delayed Sertoli cell
maturation in rats treated with prophylthiour acyl: evidence that the Sertoli cell controls testis growth. Anat.
Rec. 242, 57 – 69.
Gultekin, F., Delibas, N., Yasar, S., Kilinc, I., 2001. 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. 75, 88–96
Gurunathan, S.J., Bukowske, P.J., 1998. Accumulation of chlorpyrifos on residential surfaces and toys accessible to
children. Environ. Health Perspect. 106.
Hogg, N., Sem, 1998. Reprod. Endocrinol. 16,241.
Jett, D.A., Navoa, R.V. 2000. In vitro and in vivo effects of chlorpyrifos on glutathione peroxidase and catalase in
developing rat brain. Neuro Toxicology. 21, 141–146.
Joshi, S.C., Mathur, R., Gulati, N., 2007. Testicular toxicity of chlorpyrifos (an organophosphate pesticide) in albino
rat. Toxicol. Ind. Health. 23 (7), 439–44.
Karanth, S., Liu, J., Oliver, K., Pope, C., 2004. Interactive toxicity of the organophosphorus insecticides
chlorpyriphos and methyl parathion in rats, Toxicol. Appl. Pharmacol. 196, 183–190.
Kidd, H., James, D.R., 1991. The agrochemicals handbook. 3rd ed. Cambridge, UK: Royal Society of Chemistry
Kobayashi, T., Miyazaki, T., Natori, M., Nozawa, S., 1991. Protective role of superoxide dismutase in human sperm
motility: superoxide dismutase activity and lipid peroxide in human seminal plasma and spermatozoa. Hum.
Reprod. 6, 987–91.
Kubota, K., Ohsako, S., Kurosawa, S., Takeda, K., Qing, W., Sakaue, M., Kawakami, T., Ishimura, R., Tohyama, C.,
EVects of vinclozolin administration on sperm production and testosterone biosynthetic pathway in
adult male rat. J. Reprod. Dev. 49, 403–412.
Latchoumycandane, C., Chitra, K.C., Mathur, P.P., 2002. The effects of 2,3,7,8- tetrachlorodibenzo-p-dioxin on the
mitochondrial and microsomal fractions of rat testis. Toxicol. 171, 127–35.
Layne, E.L., Coddingtan, A.B., Ramjit, H.G. and Calby, H.O. 1993. Identification of spironolactone metabolites in
plasma and target organs of guinea pig. Drug. Metabol. Dispos., 21 (6), 1086- 90.
Lee, A., East, J., Balgaug, P., 1991. Interactions of insecticides with biological membranes. Pestic. Sci. 32, 317–327.
Linn, S., 1998. DNA damage by iron and hydrogen peroxide in vitro and in vivo. Drug Metab. Rev. 30, 313–326.
Lodovici M, Aiolli S, Monsenat C, Dolara P, Medica A, Di Simplicio P. 1994. Effect of mixture of 15 commonly used
pesticides on DNA levels of 8-hydroxy-2-deoxyguanosine and xenobiotic metabolizing enzymes in rat liver. J.
Environ. Pathol. Toxicol. Oncol. 13,163–168.
Maellaro, E., Casini, A.F., Dell Bello, B., Comporti, M., 1990 . Lipid peroxidation and antioxidant systems in the liver
injury produced by glutathione depleting agents, Biochem. Pharmacol. 39, 1513–1521.
Manna. P.R., Roy, P, Clark, B.J., Stocco, D.M., Huhtaniemi, I.T., 2001a. Interaction of thyroid hormone and
steridigenic acute regulatory (StAR) protein in the regulation of murine leydig cell steroidogenesis. J. Steroid
Biochem. Mol. Biol. 76, 167–77.
Manna, P.R., Kero, J., Tena-sempere, M., Pakarinen, P., Stocco, D.M., Huhtaniemi I.T. 2001b. Assessment of
mechanisms of thyroid hormone action in mouse leydig cells: regulation of the steroidogenic acute regulatory
protein, steridogenesis, and luteinizing hormone receptors function. Endocrinol. 142, 319–31.
Marklund, S., Marklund, G., 1974. Involvement of superoxide anion radical in autooxidation of pyrogallol and a
convenient assay for superoxide dismutase. Eur. J. Biochem. 47, 469–474.
Marrs, T.C., 1993. Organophosphate poisoning, Pharmacol. Ther. 58, 51–66.
Murono, E.P., Lin, T., Osterman, J., Nankin, H.R., 1980. The effects of cytochalasin B on testosterone synthesis by
interstitial cells of rat testis. Biochem. Biophys. Acta., 633:228–36.
Mutch, E., Williams, F.M., 2007. Diazinon, Chlorpyriphos and parathion are metabolised by multiple cytochrome
P450 in human liver, Toxicol. 224, 22–32.
Narayana, K., Prashanthi, N., Nayanatara, A., Kumar, H.H., Abhilash, K., Bairy, K.L, 2006. Neonatal methyl parathion
exposure aVects the growth and functions of the male reproductive system in the adult rat. Folia. Morphol.
(Warsz) 65, 26–33.
Peltola, V., Mantalya, E., Huhtaniemi, I., Ahotupa, M., 1994. Lipid peroxidation and antioxidant enzyme activities in
the rat testis after cigarette smoke inhalation or administration of polychlorinated biphenyls or
polychlorinated naphthalenes. J. Androl. 15, 353–61.
Qiao, D., Seidler, F.J., Tate, C.A., Cousins, M.M., Slotkin, T.A., 2003. Fetal chlorpyrifos exposure: adverse effects on
brain cell development and cholinergic biomarkers emerge postnatal and continue into adolescence and
adulthood. Environ. Health perspect. 111, 536–44.
Rana, S.V.S., Allen, T., Singh, R., 2002. Inevitable glutathione, then and now.Indian J. Exp. Biol. 40,706–16.
Rawlings, N.C., Cook, S.J., Waldbillig, D., 1998. Effects of the pesticides carbofuran, chlorpyrifos, dimethoate,
lindane, triallate, trifluralin, 2,4-D, and pentachlorophenol on the metabolic endocrine and reproductive
endocrine system in ewes. J. Toxicol. Environ. Health. A; 54(1),21–36.
Richardson, R.J., Moore, T.B., Kayyali, U.S., Fowke, J.H., Randall, J.C., 1993. Inhibition of hen brain
acetylcholinesterase and neurotoxic esterase by chlorpyriphos in vivo and kinetics of inhibition by
chlorpyriphos oxon in vitro: application to assessment of neuropathic risk, Fundam. Appl. Toxicol. 20, 273–
Selvam, R., 2002. Calcium oxalate stone disease: role of lipid peroxidation and antioxidants. Urol. Res. 30, 35–47.
Setchell, B.P., (1974). Secretions of the testis and epidedymis. J. Rep. Fert. 37, 165-177.
Seven, A., Gu¨ zel, S., Seymen, O., Civelek, S., Bolayirh, M., Uncu, M., BurC¸ G., 2004. Effects of vitamin E
supplementation on oxidative stress in streptozotocin induced diabetic rats: investigation of liver and plasma.
Yonsei Med. J. 45, 703–710.
Sujatha, R., Chitra, K.C., Latchoumycandane, C., Mathur, P.P., 2001. Effect of lindane on testicular antioxidant
system and steroidogenic enzymes in adult rats. Asian J. Androl. 3, 135–8.
Suresh Babu, N., Malik, J.K., Rao, G.S., Aggarwal, M., Ranganathan, V., 2006. Effects of subchronic malathion
exposure on the pharmacokinetic disposition of pefloxacin. Environ. Toxicol. Pharmacol. 22, 167–171.
Tian, Y., Ishikawa, H., Yamaguchi, T., Yamauchi, T., Yokoyama, K., 2005. Teratogenic and developmental toxicity of
chlorpyrifos maternal exposure during organogenesis in mice. Reprod. Toxicol. 20, 267–71.
USDA, 1994. Agriculture Chemical Usage. Field Crop Study. Washington,DC, U.S. Department of Agriculture, pp.
Verma, R.S., Srivastava, N., 2001. Chlorpyrifos induced alterations in levels of thiobarbituric acid reactive
substances and glutathione in rat brain. Indian J. Exp. Biol. 39, 174–177.
Verma, R.S., Srivastava, N., 2003. Effect of chlorpyrifos on thiobarbituric acid reactive substances, scavenging
enzymes and glutathione in rat tissues. Indian J. Biochem. Biophys. 40, 423–428.
Verma, R.S., Mehta, A., Srivastava, N., 2007. In vivo chlorpyrifos induced oxidative stres: attenuation by antioxidant
vitamins. Pestic. Biochem. Phys. 88, 191–196.
Verma, R.S A., Mehta, A., Srivastava, N., (2009). Comparative studies on chlorpyrifos and methyl parathion induced
oxidative stress in different parts of rat brain: Attenuation by antioxidant vitamins. Pesticide Bioch. Physio.
Walsh, L.P., McCormick, C., Martin, C., Stocco, D.M., 2000. Roundup inhibits steroidogenesis by disrupting
steroidogenic acute regulatory (StAR) protein expression. Environ. Health Prespect. 108, 776–96.
WHO, The WHO 1997. Recommended Classification of Pesticides by Hazard 1996–1997, International Programme
on Chemical Safety, WHO/IPCS/96.3.
Yasmashita, M., Tanaka, J., Ando, Y., 1997. Human mortality in organophosphate poisonings, Vet. Hum. Toxicol.
How to Cite
Copyright (c) 2012 E. E. Elsharkawy, D. Yahia, N.A. El-Nisr
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.