Cytotoxic Synergy between Indomethacin and Hydrochloric Acid in Gastric Mucosal Cells

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 prima...

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Bibliographic Details
Published in:Biological & Pharmaceutical Bulletin 2004, Vol.27(8), pp.1188-1192
Main Authors: Tanaka, Ken-ichiro, Tomisato, Wataru, Tsutsumi, Shinji, Hoshino, Tatsuya, Tsuchiya, Tomofusa, Mizushima, Tohru
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents, Non-Steroidal - pharmacology
Apoptosis
cytotoxic synergy
Gastric Mucosa - cytology
Gastric Mucosa - drug effects
gastric mucosal cell
Guinea Pigs
hydrochloric acid
Hydrochloric Acid - pharmacology
In Vitro Techniques
indomethacin
Indomethacin - pharmacology
Male
necrosis
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Summary: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.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.27.1188