Objectives: The present study aimed to evaluate experimentally the impact of prophylactic administration of montelukast (MLK) on the ulcerogenic effect of exposure to cold-restraint stress with and without administration of dexamethasone (DXM) in rat model.
Material & Methods: The present study included 64 adult male Sprague Dawley rats divided into negative (Group I, n=8) and positive (Group II, n=8) control groups and MLK-pretreated group (Group III) included 24 rats that were pretreated with MLK and subdivided according to used MLK dose (3, 10 & 30 mg/kg p.o.), 30 minutes before the start of 3-hrs of acute cold-restraint stress. Group IV (DXM group): included 16 rats that received DXM in 2-variant doses (0.25 or 0.5 mg/kg orally), 30 minutes before the start of 3 hrs of acute cold-restraint stress and subdivided equally. Group V (MLK- pretreated DXM group): included 8 rats that received MLK (10mg/kg p.o.) concomitant with DXM (0.5mg/kg orally) 30 minutes before the start of 3 hrs of acute cold- restraint stress. Animals were immobilized in open wire restraint cages and placed at 4±1oC for 3 hours; then were sacrificed by decapitation, the stomach was excised, opened, and examined macroscopically for damage quantified using the ulceration index (UI) and the preventive index (PI) of the drug used and a stomach tissue was then used for spectrophotometric determination of the enzymatic activities of superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) level.
Results: All animals exposed to cold-restraint stress with or without DXM administrations had gastric ulcers of varied extent and severity, irrespective of the administration of MLK. However, prophylactic MLK administration in groups III and V significantly reduced UI compared to group II and IV, respectively. Prophylactic MLK administration showed a dose-dependent PI that was significantly higher in animals received MLK in a dose of 30 mg compared to those received 3 or 10 mg dose with significantly higher PI in those received 10 mg compared to those received 3 mg. Prophylactic administration of MLK significantly reduced CAT and improved SOD activities and improved GSH level in gastric tissue extract compared to animals did not receive MLK prophylaxis.
Conclusion: Prophylactic administration of MLK could ameliorate the ulcerogenic effect of variant ulcerogenic agents with high preventive index of 10 mg MLK once daily on the ulcerogenic effect of DXM. Thus, MLK administration in addition to its role as therapeutic modality for asthma patients could provide prophylaxis whenever corticosteroid therapy is indicated
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