Melatonin reduces X-ray radiation-induced lung injury in mice by modulating oxidative stress and cytokine expression

Purpose: The modification of radiation-induced lung injuries by melatonin was studied by measuring changes in oxidative stress, cytokine expression and histopathology in the lung tissue of mice following irradiation. Materials and methods: The thoraces of C57BL/6 mice were exposed to a single X-ray radiation dose of 12 Gy with or without 200 mg/kg of melatonin pretreatment. The level and localization of transforming growth factor (TGF)-beta 1 protein were measured using an enzyme-linked immunosorbent assay (ELISA) method and immunohistochemical staining, respectively. Real-time quantitative polymerase chain reaction (PCR) was established to evaluate the relative mRNA expression levels of TGF-beta 1, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and IL-6. Results: Malondialdehyde (MDA) levels increased after irradiation and then significantly reduced (1.9-fold) under melatonin treatment. Changes in superoxide dismutase (SOD) and catalase activities, as well as glutathione (GSH) levels, after irradiation were significantly reduced by melatonin, including a notable 5.4-fold difference in catalase activity. We observed increased expression of TGF-beta 1 and TNF-alpha after irradiation and a significant reduction in the elevation of their expression by melatonin treatment. Furthermore, irradiation-induced histopathologic alterations were obviously abated in the melatonin-pretreated mice. Conclusions: The present results suggest that melatonin reduces radiation-induced lung injury via a significant reduction of oxidative stress and of the production of cytokines, such as TGF-beta 1 and TNF-alpha, the production of which increased following lung irradiation.