Sener Göksel, Kabasakal Levent, Cetinel Sule, Contuk Gazi, Gedik Nursal, Yeğen Berrak C
School of Pharmacy, Department of Pharmacology, Marmara University, 34668 Haydarpaşa, Istanbul, Turkey.
Burns. 2005 Aug;31(5):587-96. doi: 10.1016/j.burns.2005.01.012.
Thermal injury elicits several systemic consequences, among them the systemic inflammatory response where the generation of reactive oxygen radicals and lipid peroxidation play important roles. In the present study, we investigated whether the leukotriene receptor blocker montelukast is protective against burn-induced remote organ injury. Under brief ether anaesthesia, shaved dorsum of the rats was exposed to 90 degrees C (burn group) or 25 degrees C (control group) water bath for 10 s. Montelukast (10 mg/kg) or saline was administered intraperitoneally immediately after and at the 12th hour of the burn injury. Rats were decapitated 24 h after burn injury and the tissue samples from lung, liver, kidney and skin were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Tissues were also examined microscopically. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels and creatinine, urea (BUN) concentrations were determined to assess liver and kidney function, respectively. Tumor necrosis factor-alpha (TNF-alpha) and lactate dehydrogenase (LDH) were also assayed in serum samples. Severe skin scald injury (30% of total body surface area) caused a significant decrease in GSH level, which was accompanied with significant increases in MDA level, MPO activity and collagen content of tissues. Similarly, serum ALT, AST and BUN levels, as well as LDH and TNF-alpha, were elevated in the burn group as compared to control group. On the other hand, montelukast treatment reversed all these biochemical indices, as well as histopathological alterations, which were induced by thermal trauma. Findings of the present study suggest that montelukast possesses an anti-inflammatory effect on burn-induced damage in remote organs and protects against oxidative organ damage by a neutrophil-dependent mechanism.
热损伤会引发多种全身后果，其中全身炎症反应中活性氧自由基的产生和脂质过氧化起着重要作用。在本研究中，我们调查了白三烯受体阻滞剂孟鲁司特是否对烧伤引起的远隔器官损伤具有保护作用。在短暂的乙醚麻醉下，将大鼠背部剃毛后分别置于90℃（烧伤组）或25℃（对照组）水浴中10秒。在烧伤后即刻及12小时腹腔注射孟鲁司特（10mg/kg）或生理盐水。烧伤后24小时将大鼠断头，取肺、肝、肾和皮肤组织样本测定丙二醛（MDA）和谷胱甘肽（GSH）水平、髓过氧化物酶（MPO）活性及胶原蛋白含量。组织也进行了显微镜检查。分别测定血清天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）水平以及肌酐、尿素（BUN）浓度以评估肝肾功能。还检测了血清样本中的肿瘤坏死因子-α（TNF-α）和乳酸脱氢酶（LDH）。严重皮肤烫伤损伤（占全身表面积的30%）导致GSH水平显著降低，同时伴有组织中MDA水平显著升高、MPO活性增强和胶原蛋白含量增加。同样，与对照组相比，烧伤组血清ALT、AST和BUN水平以及LDH和TNF-α均升高。另一方面，孟鲁司特治疗逆转了所有这些由热损伤诱导的生化指标以及组织病理学改变。本研究结果表明，孟鲁司特对烧伤引起的远隔器官损伤具有抗炎作用，并通过中性粒细胞依赖机制保护器官免受氧化损伤。
