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标题：Effect of Nitric Oxide on β-Glucan/Indomethacin-Induced Septic Shock
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作者：Sachiko Nameda ; Maki Saito ; Noriko N. Miura 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：2005
卷号：28
期号：7
页码：1254-1258
DOI：10.1248/bpb.28.1254
出版社：The Pharmaceutical Society of Japan
摘要：We have previously shown that repeated administration of nonsteroidal anti-inflammatory drugs (NSAIDs) to mice treated with β-glucan, a biological response modifier, induced severe lethality. The lethality would be strongly related to the translocation of enterobacterial flora to the peritoneal cavity and disruption of the cytokine network. Reports suggest that nitric oxide (NO) can have an effective or detrimental role in septic shock. In the present study, we examined the effect of NO, an inflammatory mediator, on β-glucan/indomethacin (IND)- induced septic shock by inhibiting its synthesis with N ^G-nitro- L -arginine methyl ester ( L -NAME), a nonselective NO synthase (NOS) inhibitor. Nitrite concentration was used as an indicator of NO generation. Mortality in β-glucan/IND-treated mice was increased by administering L -NAME. Numbers of bacteria in various organs of mice treated with β-glucan/IND rose significantly within a couple of days of the administration of L -NAME. Additionally, TNF-α, IL-1β, and IL-6 concentrations were enhanced in peritoneal exuded cells in culture. These results suggest a significant loss of the bactericidal activity of macrophages on the administration of a NOS inhibitor which enhanced the rate of enterobacterial invasion to the peritoneal cavity, resulting in systemic inflammatory response syndrome. The production of NO, therefore, provides a protective effect in β-glucan/IND-induced sepsis.
关键词：nitric oxide;β-glucan;indomethacin;bactericidal activity;NG-nitro- L -arginine methyl ester ( L -NAME)