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孟鲁司特对大鼠百草枯中毒性肺损伤的保护作用。

Protective effect of montelukast on paraquat-induced lung toxicity in rats.

机构信息

Department of pharmacology, Faculty of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

出版信息

Biosci Trends. 2009 Apr;3(2):63-72.

Abstract

In the current study, the possible protective effect of montelukast (Mont, 50 mg/kg, p.o given 2, 24, and 48 h after paraquat injection) against acute paraquat toxicity (PQ, 25 mg/kg i.p.) in rats was evaluated. The effects of treatment on selected oxidative stress parameters in lung tissues as well as certain inflammatory markers in serum were evaluated. The obtained results revealed that Mont can ameliorate the biochemical alterations in the lung tissues which were induced by PQ in rats. This was evidenced by the significant reduction in lung tissues lipid peroxidation, protein carbonyl content and DNA fragmentation, as well as by normalization of glutathione and myeloperoxidase activities. Moreover, the elevated levels of serum TNF-alpha, and LDH induced by paraquat were reversed in Mont-treated rats. Meanwhile, lung paraquat concentration was significantly reduced after Mont treatment compared with PQ alone group. Additionally, a higher survival percentage was observed in rats treated with Mont (80%) compared with the PQ alone group (30%) during 7 days observation. The results indicate that Mont protects lung tissue by balancing oxidant?antioxidant status, inhibiting neutrophil infiltration, and by regulating the generation of inflammatory mediators. In conclusion, the obtained results emphasize the beneficial effect of Mont in ameliorating the toxicity signs of paraquat in rats. The current study greatly recommends the usage of Mont in management of paraquat toxicity.

摘要

在本研究中,评估了孟鲁司特(Mont,50mg/kg,口服,在百草枯注射后 2、24 和 48 小时给予)对大鼠急性百草枯毒性(PQ,25mg/kg 腹腔注射)的可能保护作用。评估了治疗对肺组织中选定的氧化应激参数以及血清中某些炎症标志物的影响。研究结果表明,孟鲁司特可以改善 PQ 诱导的大鼠肺组织的生化改变。这表现在肺组织脂质过氧化、蛋白羰基含量和 DNA 片段的显著减少,以及谷胱甘肽和髓过氧化物酶活性的正常化。此外,孟鲁司特治疗还逆转了 PQ 诱导的血清 TNF-α和 LDH 水平升高。同时,与单独使用 PQ 组相比,孟鲁司特治疗后肺组织中的百草枯浓度显著降低。此外,在 7 天的观察期间,用孟鲁司特治疗的大鼠(80%)的存活率明显高于单独使用 PQ 组(30%)。结果表明,孟鲁司特通过平衡氧化应激状态、抑制中性粒细胞浸润和调节炎症介质的产生来保护肺组织。总之,研究结果强调了孟鲁司特在改善大鼠百草枯毒性的有益作用。本研究强烈推荐孟鲁司特用于百草枯毒性的治疗。

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