doi: 10.1111/j.1472-8206.2011.00974.x ORIGINAL ARTICLE Captopril and telmisartan treatments attenuate cadmium-induced testicular toxicity in rats Amr A. Fouad a *, Iyad Jresat b a Department of Biomedical Sciences, Pharmacology Division, College of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia b Department of Biomedical Sciences, Pathology Division, College of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia INTRODUCTION Cadmium is one of the most environmentally abundant toxic metals which adversely affects numerous body organs. Occupational exposure to cadmium occurs because of working with cadmium-containing pigments, plastics, glass, metal alloys, and electrode material in batteries. Non-occupational exposure predominantly results from smoking, air pollution, and consumption of cadmium-contaminated water and sea foods [1]. Acute and chronic cadmium toxicity is associated with severe testicular damage, in both humans and animals [2]. Previous studies demonstrated a significant decrease in testicular weights with reduced androgen secretion as a result of exposure to cadmium indicating that testic- ular endocrine function had been compromised [3,4]. Oxidative stress and inflammation are the main factors implicated in cadmium-induced tissue injury. Also, several antioxidants and anti-inflammatory agents were found to be effective in minimizing cadmium-induced testicular toxicity with restoration of testicular steroido- genesis [5–7]. Angiotensin II, the central product of renin-angioten- sin system, induces tissue oxidative stress, inflammation, and apoptosis by activating the angiotensin II type 1 (AT1) receptor [8]. Captopril, an angiotensin-converting enzyme inhibitor, decreases the circulating and tissue levels of angiotensin II. Also, as a thiol-containing compound, captopril possesses powerful antioxidant activity, scavenges different types of reactive oxygen species, and prevents lipid peroxidation [9–11]. On the other hand, telmisartan is a highly selective AT1- receptor antagonist and also acts as a partial agonist on the nuclear peroxisome proliferator-activated receptor-c Keywords cadmium toxicity, captopril, rats, telmisartan, testis Received 24 February 2011; revised 6 May 2011; accepted 4 July 2011 *Correspondence and reprints: amrfouad65@yahoo.com ABSTRACT The possible protective effect of captopril, an angiotensin-converting enzyme inhibitor, vs. telmisartan, an angiotensin II-receptor antagonist, was investigated in rats with testicular injury induced by a single i.p. injection of cadmium chloride (2 mg/kg). Captopril (60 mg/kg/day, p.o.) and telmisartan (10 mg/kg/day, p.o.) were given for five consecutive days, starting 3 days before cadmium administration. Both agents significantly increased serum testosterone level, which was reduced by cadmium, suppressed lipid peroxidation, restored the depleted reduced glutathione, decreased the elevations of nitric oxide, tumor necrosis factor-a, and cadmium ion levels, and attenuated the reductions of selenium and zinc ions in testicular tissue resulted from cadmium administration. Immunohistochemical analysis revealed that both captopril and telmisartan significantly reduced the cadmium-induced expression of inducible nitric oxide synthase, nuclear factor-jB, Fas ligand, and caspase-3 in testicular tissue. The differences between the results obtained with captopril and telmisartan were insignificant, suggesting that both drugs equally protected the testicular tissue from the detrimental effects of cadmium. ª 2011 The Authors Fundamental and Clinical Pharmacology ª 2011 Socie ´ te ´ Franc ¸aise de Pharmacologie et de The ´ rapeutique Fundamental & Clinical Pharmacology 1 Fundamental & Clinical Pharmacology