Gastroprotective and Antioxidant Effects of Montelukast on Indomethacin-Induced Gastric Ulcer in Rats

Abstract

Abstract. 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.

Beneficial Effects of Montelukast against Cisplatin-Induced Acute Renal Damage in Rats

“…It is well known that CP leads to a significant reduced antioxidant status in humans and animals. 45,46 On the other hand, in another study, Dengiz et al 47 reported that montelukast plus CP injection generally reversed the toxic effects of CP and numerically increased GSH levels. Similarly here, montelukast administration could not increase reduction of GSH levels, whereas montelukast therapy tended to ameliorate GSH enzymes to nearly the same level as controls.…”

Histopathologic evaluation of anti-ulcerogenic effect of montelukast in indomethacin-induced experimental ulcer model

“…Neutrophil infiltration into the gastric mucosal tissues is a critical process in the pathogenesis of a variety of gastric ulcers. A relationship between the anti-oxidant and anti-ulcerogenic effects of montelukast was shown in our previous study (13). The purpose of the present study was to investigate the relationship between the gastroprotective effect of montelukast and polymorphonuclear leukocytes (PMNL) infiltration in the gastric tissues.…”

“…We previously showed the anti-ulcerogenic and anti-oxidant activities of montelukast in the same ulcer model (13). In this study, we aimed to determine the relationship between the anti-ulcerogenic effects and PMNL infiltration into the gastric mucosa.…”

“…Our previous study (13) and the study of fiener et al (17) had shown that pretreatment with montelukast prevented the increase in myeloperoxidase (MPO) activity. MPO is an essential enzyme for normal neutrophil function, and is also an index of neutrophil infiltration.…”

The Evaluation of the Ameliorative Effect of Montelukast Against Arsenic Trioxide-Induced Cardiotoxicity in Rats

“…Numerous studies have shown that montelukast possesses considerable antioxidant and anti-inflammatory functions (16,25). Protective effects of montelukast against oxidative stress have been attributed to a neutrophildependent pathway, ROS scavenging properties and inhibition of caspase 3 (14,26,27).…”