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A selenocysteine derivative therapy affects radiation-induced pneumonitis in the mouse.
- Source :
-
American journal of respiratory cell and molecular biology [Am J Respir Cell Mol Biol] 2013 Oct; Vol. 49 (4), pp. 654-61. - Publication Year :
- 2013
-
Abstract
- The mechanism leading to the radiation-induced lung response of pneumonitis is largely unknown. Here we investigated whether treatment with 3,3'-diselenodipropionic acid (DSePA), which reduces radiation-induced oxidative stress in acute response models, decreases the lung response to irradiation. Mice of the C3H/HeJ (alveolitis/pneumonitis-responding) strain received 18 Gy whole-thorax irradiation, and a subset of these mice was treated with DSePA (2 mg/kg) three times per week, beginning at 2 hours after radiation treatment, and continuing in the postirradiation period until death because of respiratory distress symptoms. DSePA treatment increased the postirradiation survival time of mice by an average of 32 days (P = 0.0002). Radiation-treated and DSePA-treated mice presented lower levels of lipid peroxidation and augmented glutathione peroxidase in the lungs, compared with those levels measured in mice receiving radiation only, when mice receiving radiation only were killed because of distress symptoms, whereas catalase and superoxide dismutase levels did not show consistent differences among treatment groups. DSePA treatment decreased pneumonitis and the numbers of mast cells, neutrophils, and lymphocytes in the lungs and bronchoalveolar lavage, respectively, of irradiated mice relative to mice exposed to radiation alone. DSePA treatment also decreased the radiation-induced increase in granulocyte colony-stimulating factor levels in the bronchoalveolar lavage and lung-tissue expression of intercellular adhesion molecule-1 and E-selectin, while increasing the expression of glutathione peroxidase-4. We conclude that DSePA treatment reduces radiation-induced pneumonitis in mice by delaying oxidative damage and the inflammatory cell influx.
- Subjects :
- Animals
Bronchoalveolar Lavage
E-Selectin genetics
E-Selectin metabolism
Glutathione Peroxidase genetics
Glutathione Peroxidase metabolism
Granulocyte Colony-Stimulating Factor genetics
Granulocyte Colony-Stimulating Factor metabolism
Inflammation drug therapy
Inflammation genetics
Inflammation metabolism
Intercellular Adhesion Molecule-1
Lipid Peroxidation drug effects
Lipid Peroxidation genetics
Lung drug effects
Lung metabolism
Lung radiation effects
Lymphocytes drug effects
Lymphocytes metabolism
Lymphocytes radiation effects
Mast Cells drug effects
Mast Cells metabolism
Mast Cells radiation effects
Mice
Mice, Inbred C3H
Neutrophils drug effects
Neutrophils metabolism
Neutrophils radiation effects
Oxidative Stress drug effects
Oxidative Stress genetics
Phospholipid Hydroperoxide Glutathione Peroxidase
Propionates pharmacology
Radiation Injuries, Experimental genetics
Radiation Injuries, Experimental metabolism
Radiation Pneumonitis genetics
Radiation Pneumonitis metabolism
Selenium Compounds pharmacology
Superoxide Dismutase genetics
Superoxide Dismutase metabolism
Thorax drug effects
Thorax metabolism
Thorax radiation effects
Radiation Injuries, Experimental drug therapy
Radiation Pneumonitis drug therapy
Selenocysteine pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1535-4989
- Volume :
- 49
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- American journal of respiratory cell and molecular biology
- Publication Type :
- Academic Journal
- Accession number :
- 23721109
- Full Text :
- https://doi.org/10.1165/rcmb.2013-0095OC