title: A selenocysteine derivative therapy affects radiation-induced pneumonitis in the mouse.
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.
authors.affiliation: 1 Department of Human Genetics, Meakins-Christie Laboratories, and.
authors.forename: Amit
authors.initials: A
authors.lastname: Kunwar
authors.forename: V K
authors.initials: VK
authors.lastname: Jain
authors.forename: K I
authors.initials: KI
authors.lastname: Priyadarsini
authors.forename: Christina K
authors.initials: CK
authors.lastname: Haston
mesh_terms: D000818:Animals; D018893:Bronchoalveolar Lavage; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1; D015227:Lipid Peroxidation / Q000187:drug effects / Q000235:genetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D008809:Mice, Inbred C3H; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D011422:Propionates / Q000494:pharmacology; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D017564:Radiation Pneumonitis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D018036:Selenium Compounds / Q000494:pharmacology; D017279:Selenocysteine / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D013909:Thorax / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects
chemical_list: C524945:3,3'-diselenodipropionic acid; D019040:E-Selectin; D011422:Propionates; D018036:Selenium Compounds; D017279:Selenocysteine; D018799:Intercellular Adhesion Molecule-1; D016179:Granulocyte Colony-Stimulating Factor; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase