Tehran University of Medical Sciences Acta Medica Iranica 0044-6025 54 7 2016 07 09 422 429 EN Atefeh Aminian Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. AND Department of Pharmacology, School of Medicine, Arak University of Medical Sciences, Arak, Iran. Shiva Javadi Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Reza Rahimian Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. AND Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. Ahmad Reza Dehpour Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. AND Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. Fahimeh Asadi Amoli Department of Pathology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Payman Moghaddas Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Shahram Ejtemaei Mehr Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 2015 10 13 2016 03 10 Nephrotoxicity is a major side effect of cisplatin, a widely used chemotherapy agent. Morphine and other opioids are also used extensively in different types of cancer for the clinical management of pain associated with local or metastatic neoplastic lesions. In addition to its analgesic effects, morphine has also been reported to possess potential immunomodulatory and antioxidant properties. Herein, we investigated the effects of morphine in a rat model of cisplatin-induced nephrotoxicity. Following administration of a single dose of cisplatin (5 mg/kg), animals received intraperitoneal injections of morphine (5 mg/kg/day) and/or naltrexone (20 mg/kg/day), an opioid antagonist, for 5 days. Cisplatin-induced nephrotoxicity was detected by a significant increase in plasma urea and creatinine levels in addition to alterations in kidney tissue morphology. Levels of TNF-α and IL-1β were significantly increased in the renal tissue in cisplatin group. Moreover, glutathione (GSH) concentration and superoxide dismutase activity were significantly reduced in renal tissue in cisplatin group compared with control animals. Treatment with morphine aggravated the deleterious effects of cisplatin at clinical, biochemical and histopathological levels; whereas naltrexone diminished the detrimental effects of morphine in animals receiving morphine and cisplatin. Morphine or naltrexone alone had no effect on the mentioned parameters. Our findings indicate that concomitant treatment with morphine might intensify cisplatin-induced renal damage in rats. These findings suggest that morphine and other opioids should be administered cautiously in patients receiving cisplatin chemotherapy. https://acta.tums.ac.ir/index.php/acta/article/view/4963 https://acta.tums.ac.ir/index.php/acta/article/download/4963/4809