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 journalArticle

1 Citation (Scopus)

Abstract

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
Volume27
Issue number8
DOIs
Publication statusPublished - 2004 Aug
Externally publishedYes

Fingerprint

Gastric Acid
Indomethacin
Hydrochloric Acid
Stomach
Irritants
Anti-Inflammatory Agents
Apoptosis
Prostaglandin-Endoperoxide Synthases
Gastric Mucosa
Pharmaceutical Preparations
Inhibitory Concentration 50
Prostaglandins
Guinea Pigs
Cell Death
Necrosis

Keywords

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

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Tanaka, K. I., Tomisato, W., Tsutsumi, S., Hoshino, T., Tsuchiya, T., & Mizushima, T. (2004). Cytotoxic synergy between indomethacin and hydrochloric acid in gastric mucosal cells. Biological and Pharmaceutical Bulletin, 27(8), 1188-1192. https://doi.org/10.1248/bpb.27.1188

Cytotoxic synergy between indomethacin and hydrochloric acid in gastric mucosal cells. / Tanaka, Ken Ichiro; Tomisato, Wataru; Tsutsumi, Shinji; Hoshino, Tatsuya; Tsuchiya, Tomofusa; Mizushima, Tohru.

In: Biological and Pharmaceutical Bulletin, Vol. 27, No. 8, 08.2004, p. 1188-1192.

Research output: Contribution to journalArticle

Tanaka, KI, Tomisato, W, Tsutsumi, S, Hoshino, T, Tsuchiya, T & Mizushima, T 2004, 'Cytotoxic synergy between indomethacin and hydrochloric acid in gastric mucosal cells', Biological and Pharmaceutical Bulletin, vol. 27, no. 8, pp. 1188-1192. https://doi.org/10.1248/bpb.27.1188
Tanaka, Ken Ichiro ; Tomisato, Wataru ; Tsutsumi, Shinji ; Hoshino, Tatsuya ; Tsuchiya, Tomofusa ; Mizushima, Tohru. / Cytotoxic synergy between indomethacin and hydrochloric acid in gastric mucosal cells. In: Biological and Pharmaceutical Bulletin. 2004 ; Vol. 27, No. 8. pp. 1188-1192.
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