Aminian Atefeh, Javadi Shiva, Rahimian Reza, Dehpour Ahmad Reza, Asadi Amoli Fahimeh, Moghaddas Payman, Ejtemaei Mehr Shahram
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.
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Acta Med Iran. 2016 Jul;54(7):422-9.
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.
肾毒性是顺铂（一种广泛使用的化疗药物）的主要副作用。吗啡和其他阿片类药物也广泛用于不同类型的癌症，用于临床管理与局部或转移性肿瘤病变相关的疼痛。除了其镇痛作用外，据报道吗啡还具有潜在的免疫调节和抗氧化特性。在此，我们研究了吗啡在顺铂诱导的肾毒性大鼠模型中的作用。在给予单剂量顺铂（5 mg/kg）后，动物接受腹腔注射吗啡（5 mg/kg/天）和/或纳曲酮（20 mg/kg/天，一种阿片类拮抗剂），持续5天。通过血浆尿素和肌酐水平的显著升高以及肾组织形态的改变来检测顺铂诱导的肾毒性。顺铂组肾组织中TNF-α和IL-1β水平显著升高。此外，与对照动物相比，顺铂组肾组织中的谷胱甘肽（GSH）浓度和超氧化物歧化酶活性显著降低。吗啡治疗在临床、生化和组织病理学水平上加重了顺铂的有害作用；而纳曲酮减轻了吗啡对接受吗啡和顺铂的动物的有害影响。单独使用吗啡或纳曲酮对上述参数没有影响。我们的研究结果表明，吗啡联合治疗可能会加重顺铂诱导的大鼠肾损伤。这些发现表明，在接受顺铂化疗的患者中，应谨慎使用吗啡和其他阿片类药物。
