Sadeghi-Hashjin G, Nijkamp F P, Henricks P A J, Folkerts G
Dept of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands.
Eur Respir J. 2002 Oct;20(4):867-72. doi: 10.1183/09031936.02.00382002.
The effects of two mast cell stabilisers, sodium cromoglycate (SCG) and doxantrazole, on the formation of reactive oxygen species (ROS) were studied. Guinea-pig alveolar macrophages (AMs) generated lucigenin-dependent chemiluminescence (LDCL). This was increased when the cells were stimulated by phorbol myristate acetate (PMA) or zymosan (by 133% and 464%, respectively, in total LDCL over 60 min). SCG decreased PMA-induced LDCL at higher concentrations (10 mM, by 55%) than doxantrazole (1 mM, by 75%). SCG decreased radical production by AMs in response to zymosan in a concentration-dependent manner by < or = 72%. Doxantrazole (0.1-1 mM) diminished total LDCL by 30-80%. In addition, glucose oxidase led to LDCL generation when incubated with glucose in a cell-free medium. This was inhibited by 47-83% in the presence of SCG or doxantrazole. SCG and doxantrazole inhibited the hydrogen peroxide- and peroxynitrite-induced LDCL by < or = 92%. Moreover, these drugs slightly increased the survival rate of the AMs. It is concluded that doxantrazole- and sodium cromoglycate-inhibited lucigenin-dependent chemiluminescence production by guinea-pig alveolar macrophages is due to a direct scavenging effect on reactive oxygen species. Doxantrazole is approximately 10-times more potent. Mast cell stabilisers may be effective in allergic asthma not only by preventing the allergen-induced mediator release, but also by preventing radical-induced lung damage.
研究了两种肥大细胞稳定剂色甘酸钠（SCG）和多克沙唑对活性氧（ROS）形成的影响。豚鼠肺泡巨噬细胞（AMs）产生了光泽精依赖性化学发光（LDCL）。当细胞受到佛波酯（PMA）或酵母聚糖刺激时，这种化学发光会增加（在60分钟内，总LDCL分别增加133%和464%）。SCG在比多克沙唑更高的浓度（10 mM，降低55%）下降低了PMA诱导的LDCL（1 mM，降低75%）。SCG以浓度依赖性方式使AMs对酵母聚糖产生的自由基减少≤72%。多克沙唑（0.1 - 1 mM）使总LDCL降低30 - 80%。此外，葡萄糖氧化酶在无细胞培养基中与葡萄糖孵育时会导致LDCL产生。在存在SCG或多克沙唑的情况下，这种化学发光被抑制47 - 83%。SCG和多克沙唑对过氧化氢和过氧亚硝酸盐诱导的LDCL的抑制作用≤92%。此外，这些药物略微提高了AMs的存活率。结论是，多克沙唑和色甘酸钠抑制豚鼠肺泡巨噬细胞的光泽精依赖性化学发光产生是由于对活性氧的直接清除作用。多克沙唑的效力约为色甘酸钠的10倍。肥大细胞稳定剂可能不仅通过防止变应原诱导的介质释放，还通过防止自由基诱导的肺损伤而对过敏性哮喘有效。
