Role of Oxidative Stress in the Radiation-Induced Lung Pathogenesis in Mice

  • Park, Eun-Mi (Division of Chemistry and Biology, University of Incheon) ;
  • Park, Ji-Sun (Division of Chemistry and Biology, University of Incheon) ;
  • Kim, Yun-Jeong (Division of Chemistry and Biology, University of Incheon) ;
  • Sung, Jae-Suk (Division of Chemistry and Biology, University of Incheon) ;
  • Hwamg, Tea-Sook (Department of Pathology, Inha University College of Medicine) ;
  • Kim, Woo-Chul (Department of Radiation Oncology, Inha University College of Medicine) ;
  • Han, Mi-Young (Green Cross Institute of Medical Genetics) ;
  • Park, Young-Mee (Division of Chemistry and Biology, University of Incheon)
  • Received : 2001.07.23
  • Accepted : 2001.09.15
  • Published : 2001.11.30

Abstract

In pre-transplant total-body irradiation (TBI), the lung is a critical dose-limiting organ. Also, the possible role of oxidative stress was suggested in the development of TBI-induced lung damage. This study explores the association between TBI-induced oxidative stress and the induction of lung pathogenesis by investigating TBI-induced oxidative stress in the lungs of male C57BL/6 mice after a single dose of 10 Gy TBI. We showed significant increases of reactive oxygen species (ROS) formation and lipid peroxidation, and also a depletion and oxidation of glutathione after TBI. There is evidence that pretreatment with 1,10-phenanthroline (o-phen) significantly reduces oxidative stress in the lung. This indicates that the TBI-induced ROS generation involves a metal-catalyzed Fenton-type reaction. A pretreatment of buthionine sulfoximine (BSO) augmented the glutathione depletion and oxidation, but had no effect on the ROS formation and lipid peroxidation up to 6 h after TBI. Histopathological features that are consistent with pneumonitis were observed in the BSO pretreated-mice 1 week after irradiation. The results suggest that TBI-induced oxidative stress in the lung involves a generation of ROS through a Fenton-type reaction. Also, glutathione plays an important inhibitory role in the radiation-induced lung pathogenesis by participating in the self-amplifying cascade subsequent to the ROS generation by irradiation.

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