RESUMO
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.