文章基本信息

标题：Cytotoxic Synergy between Indomethacin and Hydrochloric Acid in Gastric Mucosal Cells
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作者：Ken-ichiro Tanaka ; Wataru Tomisato ; Shinji Tsutsumi 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2004
卷号：27
期号：8
页码：1188-1192
DOI：10.1248/bpb.27.1188
出版社：The Pharmaceutical Society of Japan
摘要：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 μ M ) did not induce apoptosis; however, hydrochloric acid-induced apoptosis was stimulated in the presence of indomethacin (50—200 μ M ). 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 n M , the synergistic response between indomethacin and hydrochloric acid appears to be independent of the inhibition of cyclooxygenase activity by indomethacin.
关键词：cytotoxic synergy;hydrochloric acid;indomethacin;gastric mucosal cell;apoptosis;necrosis