Chlorpyrifos Induced Testicular Damage in Rats: Ameliorative Effect of Glutathione Antioxidant Eman E. Elsharkawy, 1 Doha Yahia, 1 Neveen A. El-Nisr 2 1 Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Assiut University, Egypt 2 International Animal Health Institute of Research- Assiut branch-Egypt, Egypt Received 9 January 2012; revised 15 October 2012; accepted 20 October 2012 ABSTRACT: This study investigated the induction of oxidative stress in the testes of adult rats exposed to chlorpyrifos (CPF). CPF was administered orally, in a dose of 30 mg/kg body weight to male rats for 90 days, twice weekly. Coadministration of water-soluble nonenzymatic antioxidant glutathione (GSH) was performed in a dose of 100 mg/kg body weight, orally, for the same period. Another two groups of male rats were administered GSH and corn oil, respectively. The activities of superoxide dismutase and GSH reductase were decreased while the levels of lipid peroxidation were increased in the testicular tissues of the exposed animals. Testosterone level in the serum was significantly decreased. A decrease in the histochemical determination of testicular alkaline phosphatase was observed in CPF-treated rats. A signif- icant decrease in all stages of spermatogenesis in the seminiferous tubules was recorded in the exposed animals. Coadministration of GSH restored these parameters. # 2012 Wiley Periodicals, Inc. Environ Toxicol 00: 000–000, 2012. Keywords: chlorpyrifos; testosterone; alkaline phosphatase; oxidative stress; spermatogenesis INTRODUCTION Occupational exposure to pesticides is becoming a common and increasingly alarming worldwide phenomenon. Approximately 3 million acute poisonings and 220 000 deaths from pesticide exposure have been reported annually (Marrs, 1993; USDA, 1994; Yamashita et al., 1997). The health effects caused by this occupational exposure are enormous. The widespread use of organophosphorus com- pounds (OP) and the high rates of food contamination could lead to humans, animals, and birds being exposed to high levels of these pesticide chemicals (Babu et al., 2006). Chlorpyrifos (CPF), O,O-diethyl-O-(3,5,6-trichloro-2-pyri- dinyl) phosphorothioate, is classified as a moderately hazardous, Class II insecticide by the World Health Organization (1997). It belongs to the phosphorothioate class of insecticides. Its acute toxicity varies according to the species and route of exposure; acute oral LD50 for male rats is estimated to be 80 mg/kg bodyweight (Karanth et al., 2004). The chief mechanism of action of OP pesticides is via the inhibition of neuronal cholinesterase, a key enzyme that is involved in neurotransmission (Richardson et al., 1993). Pesticides are known to produce oxidative stress, and extensive data suggest that oxygen free-radical forma- tion can be a major contributor to the toxicity of pesticides (Lodovici et al., 1994; Bagchi et al., 2002). Many insecti- cides are hydrophobic molecules that bind extensively to biological membranes, especially phospholipid bilayers, and they may damage the membranes by inducing lipid per- oxidation (LPO) (Lee et al., 1991). Some OP pesticides have also been reported to affect the reproductive system (Farag et al., 2000). CPF can have adverse effects on repro- ductive performance, and showed fetotoxic and teratogenic Correspondence to: E. E. Elsharkawy; medicine1971@yahoo.com Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/tox.21831  C 2012 Wiley Periodicals, Inc. 1