Dengiz Gunnur Ozbakis, Odabasoglu Fehmi, Halici Zekai, Cadirci Elif, Suleyman Halis
Department of Pharmacology, Faculty of Medicine, Karaelmas University, Turkey.
J Pharmacol Sci. 2007 Sep;105(1):94-102. doi: 10.1254/jphs.fp0070122.
Montelukast, a selective reversible cysteinyl leukotriene D(4)-receptor (LTD(4) receptor) antagonist, is used in the treatment of asthma. We have investigated alterations in the glutathione (GSH) and activity levels of antioxidative enzymes [superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and glutathione reductase (GR)] and myeloperoxidase (MPO), as markers of the ulceration process following oral administration of montelukast, lansoprazole, famotidine, and ranitidine, respectively, in rats with indomethacin-induced ulcers. In the present study, we found that 1) montelukast, lansoprazole, famotidine, and ranitidine all reduced the development of indomethacin-induced gastric damage, with this reduction occurring at a greater magnitude for montelukast, famotidine, and lansoprazole than for ranitidine; 2) montelukast and ranitidine both alleviated increases in the activity levels of CAT and GST enzymes resulting from gastric injury; 3) montelukast and ranitidine both ameliorated depressions in the GSH and activity levels of SOD and GR enzymes caused by indomethacin administration; and 4) all doses of montelukast, lansoprazole, and ranitidine decreased amplification of MPO activity resulting from induced gastric injuries. These results suggest that the gastroprotective effects of montelukast on indomethacin-induced ulcerations can be attributed to its ameliorating effect on oxidative damage and MPO activity.
孟鲁司特是一种选择性可逆半胱氨酰白三烯D4受体（LTD4受体）拮抗剂，用于治疗哮喘。我们研究了谷胱甘肽（GSH）、抗氧化酶[超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽S-转移酶（GST）和谷胱甘肽还原酶（GR）]以及髓过氧化物酶（MPO）的活性水平变化，这些变化作为分别口服孟鲁司特、兰索拉唑、法莫替丁和雷尼替丁后，吲哚美辛诱导的大鼠溃疡形成过程的标志物。在本研究中，我们发现：1）孟鲁司特、兰索拉唑、法莫替丁和雷尼替丁均能减轻吲哚美辛诱导的胃损伤，其中孟鲁司特、法莫替丁和兰索拉唑的减轻程度大于雷尼替丁；2）孟鲁司特和雷尼替丁均能缓解胃损伤导致的CAT和GST酶活性水平升高；3）孟鲁司特和雷尼替丁均能改善吲哚美辛给药引起的GSH、SOD和GR酶活性水平降低；4）所有剂量的孟鲁司特、兰索拉唑和雷尼替丁均能降低诱导的胃损伤导致的MPO活性增强。这些结果表明，孟鲁司特对吲哚美辛诱导的溃疡的胃保护作用可归因于其对氧化损伤和MPO活性的改善作用。
