montelukast and Stomach-Ulcer

The effects of anti-ulcerogenic drugs are dependent on the increase in prostaglandin production and reduction in leukotriene production in the gastric mucosa. Montelukast is an anti-asthmatic drug, a selective reversible cysteinyl leukotriene D4 receptor antagonist. In this study, we aimed to evaluate the anti-ulcerogenic effect of montelukast and to investigate the relationship between its anti-ulcerogenic effect and polymorphonuclear leukocyte infiltration in the gastric tissues.. Male Sprague-Dawley rats were separated into five groups. Distilled water (control group), famotidine (40 mg/kg), and montelukast (5, 10 and 20 mg/kg) were given orally (gavage). Thirty minutes later, indomethacin (25 mg/kg) was administered to all the groups. Six hours later, the animals were sacrificed by decapitation. The ulcer indexes for each stomach and the ulcer inhibition rates for each group were calculated, and the stomachs were later evaluated histopathologically (polymorphonuclear leukocyte infiltration).. Ulcer inhibition rates were as follows: famotidine 96.14% and montelukast 59.96%, 72.65% and 76.97% (5, 10 and 20 mg/kg, respectively). Montelukast (10 and 20 mg/kg) showed effects similar to those of famotidine histopathologically.. In this study, it was observed that there was a relationship between the anti-ulcerogenic effect of montelukast and polymorphonuclear leukocyte infiltration in the gastric mucosa, and montelukast behaved as an anti-ulcerogenic drug both macroscopically and microscopically.

Topics: Acetates; Animals; Anti-Ulcer Agents; Cyclopropanes; Disease Models, Animal; Famotidine; Gastric Mucosa; Indomethacin; Leukocyte Count; Leukotriene Antagonists; Male; Neutrophils; Quinolines; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Sulfides

Montelukast, a selective reversible cysteinyl leukotriene D(4)-receptor (LTD(4) receptor) antagonist, is used in the treatment of asthma. We have investigated alterations in the glutathione (GSH) and activity levels of antioxidative enzymes [superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and glutathione reductase (GR)] and myeloperoxidase (MPO), as markers of the ulceration process following oral administration of montelukast, lansoprazole, famotidine, and ranitidine, respectively, in rats with indomethacin-induced ulcers. In the present study, we found that 1) montelukast, lansoprazole, famotidine, and ranitidine all reduced the development of indomethacin-induced gastric damage, with this reduction occurring at a greater magnitude for montelukast, famotidine, and lansoprazole than for ranitidine; 2) montelukast and ranitidine both alleviated increases in the activity levels of CAT and GST enzymes resulting from gastric injury; 3) montelukast and ranitidine both ameliorated depressions in the GSH and activity levels of SOD and GR enzymes caused by indomethacin administration; and 4) all doses of montelukast, lansoprazole, and ranitidine decreased amplification of MPO activity resulting from induced gastric injuries. These results suggest that the gastroprotective effects of montelukast on indomethacin-induced ulcerations can be attributed to its ameliorating effect on oxidative damage and MPO activity.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Acetates; Animals; Anti-Ulcer Agents; Antioxidants; Catalase; Cyclopropanes; Dose-Response Relationship, Drug; Famotidine; Gastrointestinal Agents; Glutathione Reductase; Glutathione Transferase; Histamine H2 Antagonists; Indomethacin; Intubation, Gastrointestinal; Lansoprazole; Male; Molecular Structure; Peroxidase; Quinolines; Ranitidine; Rats; Rats, Sprague-Dawley; Stomach; Stomach Ulcer; Sulfides; Superoxide Dismutase

Alendronate causes serious gastrointestinal adverse effects. We aimed to investigate if montelukast, a leukotriene receptor antagonist, is protective against this damage. Rats were administered 20 mg/kg alendronate by gavage for 4 days, either alone or following treatment with montelukast (10 mg/kg). On the last day, following drug administration, pilor ligation was performed and 2 h later, rats were killed and stomach, liver and kidney tissues were removed. Gastric acidity, gastric tissue ulcer index values and malondialdehyde (MDA); an end product of lipid peroxidation, and glutathione (GSH) levels; a key antioxidant, as well as myeloperoxidase (MPO) activity; an indirect marker of tissue neutrophil infiltration were determined, and the histologic appearance of the stomach, liver and kidney tissues were studied. Chronic oral administration of alendronate induced significant gastric damage, increasing myeloperoxidase activity and lipid peroxidation, while tissue glutathione levels decreased. Similarly, in the alendronate group MDA levels and MPO activities of liver and kidney tissues were increased and GSH levels were decreased. Treatment with montelukast prevented the damage as well as the changes in biochemical parameters in all tissues studied. Findings of the present study suggest that alendronate is a local irritant that causes inflammation through neutrophil infiltration and oxidative damage in tissues, and that montelukast is protective against this damage by its anti-inflammatory effect.

Topics: Acetates; Alendronate; Animals; Cyclopropanes; Female; Gastric Acidity Determination; Gastric Mucosa; Glutathione; Hydrogen-Ion Concentration; Kidney; Leukotriene Antagonists; Liver; Male; Malondialdehyde; Peroxidase; Quinolines; Rats; Rats, Wistar; Stomach Ulcer; Sulfides