title: Enhancement of Cisplatin Nephrotoxicity by Morphine and Its Attenuation by the Opioid Antagonist Naltrexone.
abstract: 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.
authors.affiliation: 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.
authors.forename: Atefeh
authors.initials: A
authors.lastname: Aminian
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Shiva
authors.initials: S
authors.lastname: Javadi
authors.affiliation: 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.
authors.forename: Reza
authors.initials: R
authors.lastname: Rahimian
authors.affiliation: 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.
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
authors.affiliation: Department of Pathology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Fahimeh
authors.initials: F
authors.lastname: Asadi Amoli
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Payman
authors.initials: P
authors.lastname: Moghaddas
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Shahram
authors.initials: S
authors.lastname: Ejtemaei Mehr
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000139:chemically induced*; D000701:Analgesics, Opioid / Q000009:adverse effects; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001806:Blood Urea Nitrogen; D002945:Cisplatin / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009020:Morphine / Q000009:adverse effects*; D009271:Naltrexone / Q000009:adverse effects*; D009292:Narcotic Antagonists / Q000009:adverse effects*; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D000970:Antineoplastic Agents; D053583:Interleukin-1beta; D009292:Narcotic Antagonists; D014409:Tumor Necrosis Factor-alpha; D009271:Naltrexone; D009020:Morphine; D003404:Creatinine; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; D002945:Cisplatin
keywords: Antioxidant; Cisplatin; Immunomodulatory; Morphine; Naltrexone; Nephrotoxicity