好中球エラスターゼ阻害薬であるシベレスタットはゲフィチニブ、ナフタレンが引き起こすマウスの急性肺障害を軽減する

DOI 機関リポジトリ (HANDLE) NDLデジタルコレクション

書誌事項

タイトル
好中球エラスターゼ阻害薬であるシベレスタットはゲフィチニブ、ナフタレンが引き起こすマウスの急性肺障害を軽減する
タイトル別名
  • Neutrophil elastase inhibitor sivelestat ameliorates gefitinib-naphthalene-induced acute pneumonitis in mice
著者
三雲, 大功
著者別名
  • Mikumo, Hironori
  • ミクモ, ヒロノリ
学位授与大学
九州大学
取得学位
博士（医学）
学位授与番号
17102甲第13689号
学位授与年月日
2017-09-25

説明

Gefitinib, 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. C57BL/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. Sivelestat 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. These results indicate that sivelestat is a promising therapeutic agent for severe acute pneumonitis caused by gefitinib.

目次

2018-03-04 再収集

2018-06-04 再収集

2023-09-01 再収集

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