Cytotoxic synergy between indomethacin and hydrochloric acid in gastric mucosal cells

Ken Ichiro Tanaka, Wataru Tomisato, Shinji Tsutsumi, Tatsuya Hoshino, Tomofusa Tsuchiya, Tohru Mizushima

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


Orally ingested non-steroidal anti-inflammatory drugs (NSAIDs) and acid in gastric secretions are gastric irritants that co-exist at the surface of the gastric mucosa. Here, we examined the individual and combined effects of indomethacin, a typical NSAID, and hydrochloric acid on cell death in primary cultures of guinea pig gastric mucosal cells. Indomethacin alone (at concentrations less than 200 μM) did not induce apoptosis; however, hydrochloric acid-induced apoptosis was stimulated in the presence of indomethacin (50-200 μM). Isobologram analysis confirmed the presence of a cytotoxic synergy between indomethacin and hydrochloric acid. The synergistic response between the two gastric irritants was also observed for necrosis. Given that the IC50 value of indomethacin for inhibition of prostaglandin synthesis is about 5 nM, the synergistic response between indomethacin and hydrochloric acid appears to be independent of the inhibition of cyclooxygenase activity by indomethacin.

Original languageEnglish
Pages (from-to)1188-1192
Number of pages5
JournalBiological and Pharmaceutical Bulletin
Issue number8
Publication statusPublished - 2004 Aug


  • Apoptosis
  • Cytotoxic synergy
  • Gastric mucosal cell
  • Hydrochloric acid
  • Indomethacin
  • Necrosis

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science


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