Melatonin ameliorates ionizing radiation-induced oxidative organ damage in rats

Abstract

This study was designed to study the effects of the potential radioprotective properties of pharmacological doses of melatonin against organ damage induced by whole-body irradiation (IR) in rats. A total of 32 male Sprague-Dawley rats were exposed to irradiation performed with a LINAC producing 6 MV photons at a focus 100 cm distant from the skin. Under ketamine anaesthesia, each rat received a single whole-body dose of 800 cGy. Immediately before and after IR, rats were treated with either saline or melatonin (20 mg/kg and 10 mg/kg, ip) and decapitated at 12-h after exposure to irradiation. Another group of rats was followed for 72-h after IR, where melatonin (10 mg/kg, ip) injections were repeated once daily. Tissue levels of malondialdehyde (MDA)an index of lipid peroxidation-, glutathione (GSH)-a key to antioxidant- and myeloperoxidase (MPO) activity-an index of neutrophil infiltration-were estimated in liver, lung, colon and intestinal tissues. The results demonstrate that both 12-h and 72-h following IR, tissue leves of MDA were elevated (p<0.05-0.001), while GSH levels were reduced (p<0.05-0.001) in all organs. On the other hand, melatonin, reduced the levels of MDA and increased the GSH levels significantly, (p<0.05-0.001). MPO activity was increased significantly in the colonic tissue at the both 12-h and 72-h, and in the hepatic tissue at the 72-h following IR, which were reduced by melatonin (p<0.01-0.001). In the lung tissue enzyme activity was decreased at 72nd h of postirradiation. In conclusion, the increase in MDA levels and MPO activity and the concomitant decrease in GSH levels demonstrate the role of oxidative mechanisms in irradiation-induced tissue damage, and melatonin, by its free radical scavenging and antioxidant properties, ameliorates irradiation-induced organ injury. Thus, supplementing cancer patients with adjuvant therapy of melatonin may have some benefit for successful radiotherapy. (C) 2003 Elsevier Inc. All rights reserved.