NSAIDs induce both necrosis and apoptosis in guinea pig gastric mucosal cells in primary culture

Wataru Tomisato, Shinji Tsutsumi, Kazuhito Rokutan, Tomofusa Tsuchiya, Tohru Mizushima

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

A major clinical problem encountered with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin is gastropathy. In this study, we examined, using guinea pig gastric mucosal cells in primary culture, how NSAIDs damage gastric mucosal cells. The short-term treatment of cells with high concentrations of indomethacin decreased cell viability in the absence of apoptotic DNA fragmentation, chromatin condensation, or caspase activation. Cells lost membrane integrity with this short-term indomethacin treatment, suggesting that indomethacin induced necrosis under these conditions. In contrast, the long-term treatment of cells with low concentrations of indomethacin decreased cell viability and was accompanied by apoptotic DNA fragmentation, chromatin condensation, and caspase activation. Pretreatment of cells with inhibitors of caspases or protein synthesis suppressed cell death caused by long-term indomethacin treatment, suggesting that apoptosis was induced when the inhibitors were not present. These results imply that NSAIDs cause gastric mucosal damage through both necrosis and apoptosis of gastric mucosal cells.

Original languageEnglish
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume281
Issue number4 44-4
Publication statusPublished - 2001
Externally publishedYes

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Primary Cell Culture
Indomethacin
Stomach
Guinea Pigs
Anti-Inflammatory Agents
Necrosis
Apoptosis
Pharmaceutical Preparations
Gastrointestinal Agents
DNA Fragmentation
Caspases
Chromatin
Cell Survival
Caspase Inhibitors
Cell Death
Cell Membrane
Proteins

Keywords

  • Aspirin
  • Caspases
  • Cell death
  • Gastric mucosal injury
  • Indomethacin

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology
  • Physiology (medical)

Cite this

NSAIDs induce both necrosis and apoptosis in guinea pig gastric mucosal cells in primary culture. / Tomisato, Wataru; Tsutsumi, Shinji; Rokutan, Kazuhito; Tsuchiya, Tomofusa; Mizushima, Tohru.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 281, No. 4 44-4, 2001.

Research output: Contribution to journalArticle

Tomisato, Wataru ; Tsutsumi, Shinji ; Rokutan, Kazuhito ; Tsuchiya, Tomofusa ; Mizushima, Tohru. / NSAIDs induce both necrosis and apoptosis in guinea pig gastric mucosal cells in primary culture. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2001 ; Vol. 281, No. 4 44-4.
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