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Updated: May 14, 2026
Monitoring Neutrophil Elastase and Cathepsin G Activity in Human Sputum Samples
Published on: May 21, 2021
Sivelestat sodium hydrate reduces radiation-induced lung injury in mice by inhibiting neutrophil elastase
Nobuhiko Yoshikawa1, Taisuke Inomata, Yoshikatsu Okada
1Department of Radiology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan. rad101@poh.osaka-med.ac.jp
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.
Insights
Sivelestat, a neutrophil elastase (NE) inhibitor, effectively reduced radiation-induced lung injury in mice. This protective effect was achieved by suppressing NE activity and mitigating inflammatory responses.
Area of Science:
- Radiation oncology
- Pulmonary medicine
- Pharmacology
Background:
- Radiation therapy for thoracic malignancies can cause significant lung damage.
- Neutrophil elastase (NE) plays a key role in inflammatory processes contributing to lung injury.
- Developing effective countermeasures against radiation-induced lung injury (RILI) is crucial for improving patient outcomes.
Purpose of the Study:
- To evaluate the efficacy of sivelestat, a selective neutrophil elastase (NE) inhibitor, in mitigating radiation-induced lung injury (RILI) in a murine model.
- To investigate the impact of sivelestat administration timing on its protective effects against RILI.
- To assess the role of NE activity in the pathogenesis of RILI.
Main Methods:
- C57BL/6J mice were subjected to 20 Gy whole-lung irradiation.
- Sivelestat was administered at different time points before and after irradiation.
- Neutrophil elastase (NE) activity was measured at 24 and 48 hours post-irradiation.
- Histopathological examination of lung tissue was performed at 24 hours, 48 hours, and 15 weeks post-irradiation to score lung damage.
Main Results:
- Sivelestat administration significantly suppressed NE activity in irradiated mice up to 48 hours post-irradiation.
- Histopathological scoring revealed significantly reduced lung damage in mice treated with sivelestat (groups RE2 and RE4) compared to the irradiated control group (group R) at 15 weeks.
- Sivelestat demonstrated a dose- and time-dependent protective effect on lung tissue.
Conclusions:
- Sivelestat effectively mitigates radiation-induced lung injury in mice.
- The protective mechanism involves the suppression of neutrophil elastase (NE) activity and subsequent reduction in inflammatory reactions.
- Sivelestat represents a potential therapeutic agent for preventing or treating radiation-induced lung injury.
