Objective and design

Montelukast, a cysteinyl leukotriene receptor antagonist, exhibits antiinflammatory action. We tested whether exposure to montelukast plus nonsteroidal antiinflammatory drugs (NSAIDs) elicits better control of paw inflammation in the rat formalin test and improves associated gastric damage.

Materials

A total of 46 adult male rats were used in the study.

Treatments

We evaluated separate and combined effects of montelukast (20 mg/kg), celecoxib (COX2 inhibitor, 10 mg/kg), and diclofenac (nonselective COX1/COX2 inhibitor, 10 mg/kg) on paw and gastric damage in the rat formalin test.

Results

Individual pretreatments of rats with montelukast, diclofenac, or celecoxib partly reduced formalin-induced increases in (i) paw edema, fibrosis, and inflammatory cells, (iii) serum interleukin-6 (IL-6) and leukotrienes (LTB4 and LTD4), and (iv) paw expressions of inducible nitric oxide synthase (iNOS) and COX2. These effects were accentuated in rats treated with montelukast plus diclofenac or montelukast plus celecoxib. Alternatively, montelukast or celecoxib, but not diclofenac, alleviated formalin-evoked gastric damage and increments in tumor necrosis factor-α and decrements in prostaglandin-E₂. These advantageous gastric influences were potentiated in rats treated with montelukast plus celecoxib.

Conclusions

While montelukast equally enhances antiinflammatory action of diclofenac or celecoxib via downregulating iNOS/COX2/LTs/IL-6 signaling, its gastroprotective action is preferentially potentiated by celecoxib.

中文翻译：

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孟鲁司特在大鼠爪福尔马林模型中增强 NSAIDs 的抗炎作用，同时将胃损伤风险降至最低

目标与设计

孟鲁司特是一种半胱氨酰白三烯受体拮抗剂，具有抗炎作用。我们测试了在大鼠福尔马林试验中暴露于孟鲁司特加非甾体抗炎药 (NSAID) 是否能更好地控制爪子炎症并改善相关的胃损伤。

材料

该研究共使用了 46 只成年雄性大鼠。

治疗

我们在大鼠福尔马林试验中评估了孟鲁司特（20 mg/kg）、塞来昔布（COX2抑制剂，10 mg/kg）和双氯芬酸（非选择性COX1/COX2抑制剂，10 mg/kg）对爪子和胃部损伤的单独和联合作用.

结果

用孟鲁司特、双氯芬酸或塞来昔布对大鼠进行个体预处理部分减少了福尔马林诱导的 (i) 爪水肿、纤维化和炎症细胞，(iii) 血清白细胞介素 6 (IL-6) 和白三烯 (LTB4 和 LTD4) 的增加， (iv) 诱导型一氧化氮合酶 (iNOS) 和 COX2 的爪子表达。这些作用在用孟鲁司特加双氯芬酸或孟鲁司特加塞来昔布治疗的大鼠中更加突出。或者，孟鲁司特或塞来昔布，但不是双氯芬酸，减轻福尔马林诱发的胃损伤和肿瘤坏死因子-α的增加和前列腺素-E _{2 的}减少。这些有利的胃影响在用孟鲁司特加塞来昔布治疗的大鼠中得到加强。

结论

虽然孟鲁司特通过下调 iNOS/COX2/LTs/IL-6 信号传导同样增强双氯芬酸或塞来昔布的抗炎作用，但塞来昔布优先增强其胃保护作用。