Morphine aggravates cisplatin-induced nephrotoxicity and oxidative stress in rats
Atefeh Aminian, Shiva Javadi, Reza Rahimian, Payman Moghaddas and Ahmad Reza Dehpour
Tehran University of Medical Sciences, Iran
Arak University of Medical Sciences, Iran
: J Pharm Drug Deliv Res
Abstract
Cisplatin is a widely used cancer therapy agent, causes major side effects in normal tissues, particularly nephrotoxicity. Morphine is extensively used for the clinical management of cancer pain. In addition to analgesic effect, various studies suggest that morphine might possess prominent immunomodulatory and antioxidant properties. In this study, we investigated the morphine effects on nephrotoxicity induced by cisplatin in rats. An i.p single dose of cisplatin(5mg/kg) was used for nephrotoxicity induction . For providing steady state plasma levels of morphine and naltrexone, an opioid antagonist, the daily doses of 5 mg/ kg and 20 mg/ kg respectively were employed for 5 days. Cisplatin- induced nephrotoxicity characterized by a significant increase in plasma urea and creatinine levels in addition to severe alterations in kidney tissue architecture. Glutathione (GSH) concentration and superoxide dismutase activity as well as TNF-α and IL-1β levels of renal tissue in cisplatin-treated rats were significantly different compared with control group. Treatment with morphine markedly aggravated the deleterious effects of cisplatin on both biochemical and histopathological parameters, whereas naltrexone masked the detrimental effects of morphine in naltrexone + morphine + cisplatin group. Morphine or naltrexone alone had no effect on the mentioned parameters. Our findings indicate that morphine worsened cisplatin-induced renal damage in rats, suggesting that its toxic effects should be kept in mind in cancer patients receiving cisplatin chemotherapy. Furthermore, our results suggest that other opioid analgesic should also be used more cautiously owing to the role of opioid receptors in mediating these adverse effects.
Biography
Email: atefeh.aminian@yahoo.com
