論文

査読有り 国際誌
2012年3月8日

Potential role of the NADPH oxidase NOX1 in the pathogenesis of 5-fluorouracil-induced intestinal mucositis in mice.

American journal of physiology. Gastrointestinal and liver physiology
  • Masashi Yasuda
  • Shinichi Kato
  • Naoki Yamanaka
  • Maho Iimori
  • Daichi Utsumi
  • Yumeno Kitahara
  • Kazumi Iwata
  • Kuniharu Matsuno
  • Kikuko Amagase
  • Chihiro Yabe-Nishimura
  • Koji Takeuchi
  • 全て表示

302
10
開始ページ
G1133-42
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1152/ajpgi.00535.2011

Although NADPH oxidase 1 (NOX1) has been shown to be highly expressed in the gastrointestinal tract, the physiological and pathophysiological roles of this enzyme are not yet fully understood. In the present study, we investigated the role of NOX1 in the pathogenesis of intestinal mucositis induced by the cancer chemotherapeutic agent 5-fluorouracil (5-FU) in mice. Intestinal mucositis was induced in Nox1 knockout (Nox1KO) and littermate wild-type (WT) mice via single, daily administration of 5-FU for 5 days. In WT mice, 5-FU caused severe intestinal mucositis characterized by a shortening of villus height, a disruption of crypts, a loss of body weight, and diarrhea. In Nox1KO mice, however, the severity of mucositis was significantly reduced, particularly with respect to crypt disruption. The numbers of apoptotic caspase-3- and caspase-8-activated cells in the intestinal crypt increased 24 h after the first 5-FU administration but were overall significantly lower in Nox1KO than in WT mice. Furthermore, the 5-FU-mediated upregulation of TNF-α, IL-1β, and NOX1 and the production of reactive oxygen species were significantly attenuated in Nox1KO mice compared with that in WT mice. These findings suggest that NOX1 plays an important role in the pathogenesis of 5-FU-induced intestinal mucositis. NOX1-derived ROS production following administration of 5-FU may promote the apoptotic response through upregulation of inflammatory cytokines.

リンク情報
DOI
https://doi.org/10.1152/ajpgi.00535.2011
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/22403796
ID情報
  • DOI : 10.1152/ajpgi.00535.2011
  • ORCIDのPut Code : 95992102
  • PubMed ID : 22403796

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