title: Sivelestat sodium hydrate reduces radiation-induced lung injury in mice by inhibiting neutrophil elastase.
abstract: The aim of this study was to investigate whether sivelestat, a neutrophil elastase (NE) inhibitor, mitigates radiation-induced lung injury in mice. C57BL/6J mice were administered a dose of 20 Gy to the bilateral whole lungs. Sivelestat was administered immediately before and 1 h after irradiation in group RE2, and immediately before and 1, 3 and 6 h after irradiation in group RE4. Group R received irradiation without sivelestat injection. Mice that did not receive sivelestat injection or irradiation were used as controls. NE activity was measured 24 and 48 h after irradiation, and the mice were sacrificed 24 h, 48 h and 15 weeks after irradiation for histopathological examination. In groups RE2 and RE4, NE activity was significantly suppressed until 48 h after irradiation compared to group R. The degree of lung damage in each group was scored during histopathological examination. Results showed that the scores of groups RE2 and RE4 were significantly lower compared to those of group R 15 weeks after irradiation. In conclusion, sivelestat reduced radiation‑induced lung injury in the mice by suppressing NE activity and excessive inflammatory reactions.
authors: Department of Radiology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan. rad101@poh.osaka-med.ac.jp
authors: Nobuhiko
authors: N
authors: Yoshikawa
authors: Taisuke
authors: T
authors: Inomata
authors: Yoshikatsu
authors: Y
authors: Okada
authors: Taiju
authors: T
authors: Shimbo
authors: Masatsugu
authors: M
authors: Takahashi
authors: Kazuhiko
authors: K
authors: Akita
authors: Yasuo
authors: Y
authors: Uesugi
authors: Yoshifumi
authors: Y
authors: Narumi
mesh_terms: D000016:Abnormalities, Radiation-Induced / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008168:Lung / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D055370:Lung Injury / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D011837:Radiation-Protective Agents / Q000008:administration & dosage*; D013449:Sulfonamides / Q000008:administration & dosage*
chemical_list: D011837:Radiation-Protective Agents; D013449:Sulfonamides; C069195:sivelestat; D019272:Leukocyte Elastase; D005998:Glycine