Irritant-induced cyclooxygenase-2 is involved in the defense mechanism of the gastric mucosa in mice |
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Authors: | Kazumasa Miyake Taku Tsukui Ken Wada Atsushi Tatsuguchi Seiji Futagami Tetsuro Hiratsuka Kei Shinoki Tadasu Iizumi Tomonori Akamatsu Choitsu Sakamoto Masafumi Kobayashi |
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Affiliation: | (1) Third Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan, JP |
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Abstract: | Background. Endogenous and exogenous prostaglandins (PGs) have been shown to contribute to reducing the gastric injury caused by irritants given subse-quently. The aim of this study was to clarify whether cyclooxygenase-2 (COX-2) protein induced by pretreatment was involved in the prevention of subsequent ethanol-caused gastric injury in mice. Methods. Mice were pretreated with acidified ethanol or saline and then COX-2 protein expression in the stomach was immunohistochemically determined every 8 h. Mice were administered 95% ethanol 24 h after the acidified ethanol pretreatment, and gastric mucosal damage was evaluated macroscopically and histologically. The effects of NS-398 or indomethacin on the 95% ethanol-caused damage were also examined. Results. Acidified ethanol pretreatment induced COX-2 protein expression in lamina propria macrophages of the gastric mucosa, with a peak level 24 h after the pretreatment. The 95% ethanol treatment caused gastric mucosal damage. The degree of the damage was not different between mice pretreated with acidified ethanol and those pretreated with saline. However, NS-398 aggravated the ethanol-caused damage only in mice pretreated with acidified ethanol, while indomethacin aggravated the damage, evaluated histologically, irrespective of the pretreatment. Conclusions. Pretreatment-induced COX-2, in addition to COX-1, seemed to be involved in the defense mechanism through minimizing the damage caused by a subsequent irritant. Received: October 16, 2000 / Accepted: September 14, 2001 |
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Keywords: | : COX-2 cytoprotection adaptive cytoprotection gastric damage selective COX-2 inhibitor ethanol |
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