Neutrophil elastase inhibitor sivelestat ameliorates gefitinib-naphthalene-induced acute pneumonitis in mice
| Autor: | Toyoshi Yanagihara, Masako Arimura Omori, Naoki Hamada, Saiko Ogata-Suetsugu, Hironori Mikumo, Chika Ikeda Harada, Eiji Harada, Yoichi Nakanishi, Tetsuya Yokoyama, Kunihiro Suziki |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Neutrophils Kaplan-Meier Estimate Pharmacology Biochemistry chemistry.chemical_compound Leukocyte Count 0302 clinical medicine Epidermal growth factor Lung Sulfonamides medicine.diagnostic_test biology Sivelestat Gefitinib medicine.anatomical_structure Neutrophil elastase Acute Disease Absolute neutrophil count Female Bronchoalveolar Lavage Fluid medicine.drug Serine Proteinase Inhibitors Biophysics Glycine Naphthalenes 03 medical and health sciences Weight Loss medicine Animals Humans Molecular Biology Pneumonitis business.industry Cell Biology Pneumonia medicine.disease respiratory tract diseases Mice Inbred C57BL 030104 developmental biology Bronchoalveolar lavage 030228 respiratory system chemistry Immunology biology.protein Quinazolines business Leukocyte Elastase |
| DOI: | 10.1101/108464 |
| Popis: | Background and objectiveGefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), is an effective therapeutic agent for non-small cell lung cancer with EGFR mutations. It can cause severe acute pneumonitis in some patients. We previously demonstrated that mice with naphthalene-induced airway epithelial injury developed severe gefitinib-induced pneumonitis and that neutrophils played important roles in the development of the disease. This study aimed to investigate the effects of the neutrophil elastase inhibitor sivelestat on gefitinib-induced pneumonitis in mice.MethodsC57BL/6J mice received naphthalene (200 mg/kg) intraperitoneally on day 0. Gefitinib (250 or 300 mg/kg) was orally administered to mice from day −1 until day 13. Sivelestat (150 mg/kg) was administered intraperitoneally from day 1 until day 13. Bronchoalveolar lavage fluid (BALF) and lung tissues were sampled on day 14.ResultsSivelestat treatment significantly reduced the protein level, neutrophil count, neutrophil elastase activity in BALF, and severity of histopathologic findings on day 14 for mice administered with 250 mg/kg of gefitinib. Moreover, sivelestat treatment significantly improved the survival of mice administered with 300 mg/kg of gefitinib. Conclusions: These results indicate that sivelestat is a promising therapeutic agent for severe acute pneumonitis caused by gefitinib.Summary statementNeutrophil elastase inhibitor sivelestat is a promising therapeutic agent for severe acute pneumonitis caused by gefitinib. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|