title: Effects of sivelestat sodium hydrate on the reduction of radiation pneumonitis.
abstract: In this study, we irradiated the murine lung and analyzed the inhibitory effects of sivelestat sodium hydrate, a neutrophil elastase (NE) inhibitor, on lung injury in mice. Sivelestat sodium hydrate (3 mg/kg) was administered by intraperitoneal injection immediately, 3, 6, and 12 h after irradiation in groups RE-0, RE-3, RE-6, and RE-12, respectively. A control group and a group receiving radiation without sivelestat (group R) were also used. NE activity was measured 24 and 48 h after irradiation. The lungs were simultaneously extirpated and stained with hematoxylin and eosin and a naphthol AS-D chloroacetate esterase stain (N-ASDCLA). NE activity increased in the groups in which the murine lungs were irradiated. There was no increase in NE activity in the control group. Among the sivelestat-administered groups, NE activity was slightly elevated in group RE-0 and was suppressed, compared to group R, in groups RE-3, RE-6, and RE-12 at 24 h after irradiation. In the irradiated groups, intra-alveolar neutrophil infiltration, perivascular edema, and alveolar wall thickness were observed, but these changes were mild in the sivelestat-administered groups. The number of N-ASDCLA-positive cells increased in the sivelestat-administered groups, while group R had low values. This indicated that sivelestat sodium hydrate blocked the release of NE from the neutrophils in the irradiated lungs. NE plays an important role in the development of radiation-induced lung injury. Sivelestat is thus expected to decrease radiation-induced lung toxicity by suppressing NE release from neutrophils.
authors.affiliation: Department of Radiology, Osaka Medical College, Osaka 569-0855, Japan. rad089@poh.osaka-med.ac.jp
authors.forename: Taiju
authors.initials: T
authors.lastname: Shimbo
authors.forename: Taisuke
authors.initials: T
authors.lastname: Inomata
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Takahashi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tatsumi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Uesugi
authors.forename: Isamu
authors.initials: I
authors.lastname: Narabayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sonobe
mesh_terms: D000818:Animals; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000201:enzymology / Q000276:immunology / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D017564:Radiation Pneumonitis / Q000188:drug therapy* / Q000276:immunology; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D013449:Sulfonamides / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; C069195:sivelestat; D019272:Leukocyte Elastase; D005998:Glycine