Gastroprotective and antioxidant effects of montelukast on indomethacin-induced gastric ulcer in rats.
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.
Dengiz
Gunnur Ozbakis
GO
Department of Pharmacology, Faculty of Medicine, Karaelmas University, Turkey.
Odabasoglu
Fehmi
F
Halici
Zekai
Z
Cadirci
Elif
E
Suleyman
Halis
H
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology / Q000627:therapeutic use; D000085:Acetates / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002374:Catalase / Q000378:metabolism; D003521:Cyclopropanes; D004305:Dose-Response Relationship, Drug; D015738:Famotidine / Q000494:pharmacology / Q000627:therapeutic use; D005765:Gastrointestinal Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D007213:Indomethacin / Q000008:administration & dosage / Q000633:toxicity; D007441:Intubation, Gastrointestinal; D064747:Lansoprazole; D008297:Male; D015394:Molecular Structure; D009195:Peroxidase / Q000378:metabolism; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011899:Ranitidine / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*; D013440:Sulfides; D013482:Superoxide Dismutase / Q000378:metabolism
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000085:Acetates; D000897:Anti-Ulcer Agents; D000975:Antioxidants; D003521:Cyclopropanes; D005765:Gastrointestinal Agents; D006635:Histamine H2 Antagonists; D011804:Quinolines; D013440:Sulfides; D064747:Lansoprazole; D015738:Famotidine; D011899:Ranitidine; D002374:Catalase; D009195:Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; C093875:montelukast; D007213:Indomethacin