Protective Effect of Mirtazapine on Indomethacin-Induced Ulcer in Rats and Its Relationship with Oxidant and Antioxidant Parameters

Abstract

Even though there are many drugs for the treatment of gastric ulcers, these drugs sometimes cannot succeed. Since the 1950s, antidepressant drugs have been used for several non-psychiatric indications. A lot of antidepressant drugs have been shown experimentally to produce antiulcer activity in various ulcer models. This study aimed to investigate the antiulcer effects of mirtazapine and to determine its relationship with antioxidant mechanisms. The antiulcer activities of 15, 30, and 60 mg/kg mirtazapine have been investigated on indomethacin-induced ulcers in rats, and the results have been compared with that of the control group. Mirtazapine decreased the indomethacin-induced ulcers significantly at all doses used. Mirtazapine significantly increased the glutathione (GSH) level, which decreased in the control group given only indomethacin. All doses of mirtazapine significantly decreased the catalase (CAT) level in stomach tissue compared to the control. Additionally, all doses of mirtazapine reversed the decrease in the superoxide dismutase (SOD) level in the stomach tissue of control rats. And finally, all doses of mirtazapine decreased malondialdehyde (MDA) and myeloperoxidase (MPO) levels significantly compared to the control. In conclusion, the activation of enzymatic and non-enzymatic antioxidant mechanisms and the inhibition of some toxic oxidant mechanisms play a role in the antiulcer effect mechanism of mirtazapine. This new indication of mirtazapine will make it the first-choice drug in depressive patients with gastric ulcers.

Investigation of Antiulcer and Antioxidant Activity of Moclobemide in Rats

“…GSH protects gastrointestinal tissue lipids from oxidative damage. As shown in many studies, in gastric tissue damaged by indomethacin, GSH level is lowered [16,30]. GSH detoxifies hydrogen peroxide and organic acids chemically; hydrogen peroxide accumulates in the absence of GSH [31].…”

“…These 48 rats were separated into 8 groups, each consisting of 6 rats. All fasted for 24 hours, and then doses of 10, 20, 40, 80, 150 mg/kg moclobemide and 20 mg/kg famotidine [16,18] were administered by oral gavage to six of the groups. The other two groups, indomethacin control and healthy intact, were administered an equal volume of water.…”

“…Although many classic drugs are available to treat gastric ulcers, these drugs cannot have permanent treatment, and researches to find such a treatment are ongoing. In recent years, experimental studies have shown that the antidepressant drug mirtazapine is better than famotidine on the indomethacin-induced ulcer model and that its gastroprotective effect originates from its antioxidant property [16].…”

Mitigation of indomethacin-induced gastric mucosal lesions by a potent specific type V phosphodiesterase inhibitor

“…In the stomach tissue of rats given indomethacin, the level of the lipid peroxidation product, MDA, increased significantly compared to the sham operated group. Tissues exposed to oxidative stress include large amounts of toxic oxygen radicals, which induce lipid peroxidation leading to MDA formation [24,25] . The lowest MDA values were detected in the famotidine g roups.…”

“…Possible mechanisms of gastroprotection of PDE V inhibitors are increased production of tissue NO [23,[26][27][28] or increased tissue cGMP level without modifying NO content [22,25,29,30] . The NO levels are slightly elevated in vardenafil pretreated rats in our study; however, the level of NO in either of vardenafil groups did not surpass the level of NO determined in the sham group.…”