title: Melatonin reduces X-ray radiation-induced lung injury in mice by modulating oxidative stress and cytokine expression.
abstract: OBJECTIVE
  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.
  
  
  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)-β1 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-β1, tumor necrosis factor (TNF)-α, interleukin (IL)-1β 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-β1 and TNF-α 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-β1 and TNF-α, the production of which increased following lung irradiation.
authors.affiliation: Department of Radiation Oncology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Seong Soon
authors.initials: SS
authors.lastname: Jang
authors.forename: Hyeong Geug
authors.initials: HG
authors.lastname: Kim
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Lee
authors.forename: Jong Min
authors.initials: JM
authors.lastname: Han
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Park
authors.forename: Gil Ja
authors.initials: GJ
authors.lastname: Huh
authors.forename: Chang Gue
authors.initials: CG
authors.lastname: Son
mesh_terms: D000818:Animals; D001483:Base Sequence; D002374:Catalase / Q000378:metabolism; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D005978:Glutathione / Q000378:metabolism; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D055370:Lung Injury / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D008550:Melatonin