Sivelestat sodium hydrate reduces radiation-induced lung injury in mice by inhibiting neutrophil elastase

Yoshikawa,Nobuhiko; Inomata,Taisuke; Okada,Yoshikatsu; Shimbo,Taiju; Takahashi,Masatsugu; Akita,Kazuhiko; Uesugi,Yasuo; Narumi,Yoshifumi

doi:10.3892/mmr.2013.1318

Sivelestat sodium hydrate reduces radiation-induced lung injury in mice by inhibiting neutrophil elastase

Authors:
- Nobuhiko Yoshikawa
- Taisuke Inomata
- Yoshikatsu Okada
- Taiju Shimbo
- Masatsugu Takahashi
- Kazuhiko Akita
- Yasuo Uesugi
- Yoshifumi Narumi
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Affiliations: Department of Radiology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan, Department of Radiation Oncology, Faculty of Medicine, Shimane University, Izumo, Shimane 693-8501, Japan, Department of Pathology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan, Department of Radiology, Saito Yukoukai Hospital, Ibaraki, Osaka 567-0085, Japan, Department of Central Radiology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan
Published online on: February 8, 2013 https://doi.org/10.3892/mmr.2013.1318
Pages: 1091-1095

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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.

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