Low direct cytotoxicity of nabumetone on gastric mucosal cells

Yasuhiro Arai, Ken Ichiro Tanaka, Hironori Ushijima, Wataru Tomisato, Shinji Tsutsumi, Mayuko Aburaya, Tatsuya Hoshino, Kazumi Yokomizo, Keitarou Suzuki, Takashi Katsu, Tomofusa Tsuchiya, Tohru Mizushima

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Prodrugs of non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for clinical purposes because they are not harmful to the gastrointestinal mucosa. We recently showed that NSAIDs have direct cytotoxicity in NSAID-induced gastric lesions. We show here that under conditions where the NSAIDs indomethacin and celecoxib clearly induce cell death, an NSAID prodrug, nabumetone, and its active metabolite 6-methoxy-2-naphthylacetic acid (6MNA), did not have such effects. Moreover, nabumetone and 6MNA exhibited much lower membrane permeabilizing activities than did indomethacin and celecoxib. We recently reported that when an orally administered NSAID was used in combination with a low dose of intravenously administered indomethacin, the severity of gastric lesions produced in rats depended on the cytotoxicity of the orally administered NSAID. Using a similar protocol, we show here that gastric lesions were produced when the orally administered NSAID was celecoxib, but not when nabumetone was used. We thus propose that the low direct cytotoxicity of nabumetone observed in vitro is maintained in vivo, and that the use of nabumetone does not harm the gastric mucosa.

Original languageEnglish
Pages (from-to)1641-1646
Number of pages6
JournalDigestive Diseases and Sciences
Volume50
Issue number9
DOIs
Publication statusPublished - 2005 Sep 1

Keywords

  • Gastric lesions
  • Gastric mucosal cells
  • Membrane permeabilization
  • Nabumetone

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

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  • Cite this

    Arai, Y., Tanaka, K. I., Ushijima, H., Tomisato, W., Tsutsumi, S., Aburaya, M., Hoshino, T., Yokomizo, K., Suzuki, K., Katsu, T., Tsuchiya, T., & Mizushima, T. (2005). Low direct cytotoxicity of nabumetone on gastric mucosal cells. Digestive Diseases and Sciences, 50(9), 1641-1646. https://doi.org/10.1007/s10620-005-2909-x