fluvoxamine and Stomach-Ulcer

The association between stress and gastric ulcers has been well reported. This study is divided into two parts: the first part of this study is consisted of analyzing the effect of fluvoxamine administration by intracerebroventricular (ICV) and intraperitoneal (IP) injections on stress-induced gastric ulcers. The second part investigates the effect of ondansetron in influencing the protection of the gastric mucous by giving fluvoxamine to the mice before being induced with stress.. Water immersion restraint stress (WIRS) was used to induce stress. Fluvoxamine 50 and 100 mg/kg by IP injection, fluvoxamine 9.3 µg, and 18.6 µg by ICV injection 30 min before the induction of stress. Meanwhile, single drug and in combination administered to the mice, ondansetron 3 mg/kg was given by IP at 60 min, and fluvoxamine 50, 100 mg/kg orally at 30 min before stress induction.. The obtained results show fluvoxamine 50 and 100 mg/kg by IP, and fluvoxamine 18.6 µg by ICV had significantly reduced ulcer index with p<0.005, p<0.001, and p<0.005 while fluvoxamine 9.3 µg showed the insignificant result. Fluvoxamine 50 mg/kg, fluvoxamine 100 mg/kg, and ondansetron 3 mg/kg monotherapy have a significant reduction in ulcers with p<0.005, p<0.001, and p<0.05, while the combination drugs showed an insignificant reduction in ulcers.. Fluvoxamine with different administration routes and ondansetron monotherapy before stress reduce the occurrence of gastric ulcers, while the combination drugs did not increase the protective effect of the gastric mucosa.

Topics: Animals; Fluvoxamine; Gastric Mucosa; Mice; Ondansetron; Pharmaceutical Preparations; Rats, Wistar; Stomach Ulcer; Ulcer

Background Selective serotonin reuptake inhibitors (SSRIs) have recently become potential candidates for a new therapeutic approach to ulcer and gastric bleeding. Heat shock protein 70 (Hsp70) plays an important role in cellular resistance to nonsteroidal anti-inflammatory drugs (NSAIDs). However, there is lack of evidence that fluvoxamine recruits Hsp70 to affect stress-induced gastric ulcer. Therefore, we investigated the effect of fluvoxamine on NSAID- and stress-induced gastric ulcer and the possible involvement of Hsp70. Methods ICR mice were used in the study. Stress induction was made by the water-immersion-plus-restraint method. NSAID-induced gastric ulcer was produced by oral administration of indomethacin. Fluvoxamine was given orally 30 min before stress induction and indomethacin treatment. Results Stress and indomethacin treatment significantly increased the ulcer index and intraluminal bleeding score. Stress and indomethacin treatment also significantly increased the expression of Hsp70. Fluvoxamine significantly decreased the ulcer index and intraluminal bleeding in both ulcer models. Moreover, fluvoxamine further increased the expression of Hsp70 in the gastric tissue of stress- and indomethacin-treated mice. Conclusions Our results indicate that fluvoxamine may have a protective effect against stress- as well as NSAID-induced gastric ulcer. In addition, the present study suggests the possible involvement of Hsp70 in the amelioration of gastric ulcer by fluvoxamine.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Disease Models, Animal; Fluvoxamine; Gastrointestinal Hemorrhage; HSP70 Heat-Shock Proteins; Indomethacin; Male; Mice; Mice, Inbred ICR; Restraint, Physical; Selective Serotonin Reuptake Inhibitors; Stomach Ulcer; Stress, Psychological

Although many drugs are available for the treatment of gastric ulcers, often these drugs are ineffective. Many antidepressant drugs have been shown to have antiulcer activity in various models of experimental ulcer. One such drug, the antidepressant mirtazapine, has been reported to have an antiulcer effect that involves an increase in antioxidant, and a decrease in oxidant, parameters. To date, however, there is no information available regarding the antiulcer activity for a similar antidepressant, fluvoxamine. This study aimed to investigate the antiulcer effects of fluvoxamine and to determine its relationship with antioxidants.. Groups of rats fasted for 24 h received fluvoxamine (25, 50, 100 and 200 mg/kg), ranitidine (50 mg/kg) or distilled water by oral gavage. Indomethacin (25 mg/kg) was orally administered to the rats as an ulcerative agent. Six hours after ulcer induction, the stomachs of the rats were excised and an ulcer index determined. Separate groups of rats were treated with the same doses of fluvoxamine and ranitidine, but not with indomethacin, to test effects of these drugs alone on biochemical parameters. The stomachs were evaluated biochemically to determine oxidant and antioxidant parameters. We used one-way ANOVA and least significant difference (LSD) options for data analysis.. The 25, 50, 100 and 200 mg/kg doses of fluvoxamine exerted antiulcer effects of 48.5, 67.5, 82.1 and 96.1%, respectively, compared to the control rat group. Ranitidine showed an 86.5% antiulcer effect. No differences were observed in the absence of indomethacin treatment for any dose of fluvoxamine or for ranitidine. The levels of antioxidant parameters, total glutathione and nitric oxide, were increased in all fluvoxamine groups and in the ranitidine group when compared with the indomethacin-only group. In addition, fluvoxamine and ranitidine decreased the levels of the oxidant parameters, myeloperoxidase and malondialdeyhyde, in the stomach tissues of the rats when compared to indomethacin group.. We conclude that fluvoxamine has antiulcer effects, and that these occur by a mechanism that involves activation of antioxidant parameters and inhibition of some toxic oxidant parameters.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Fluvoxamine; Gastric Mucosa; Glutathione; Indomethacin; Male; Malondialdehyde; Nitric Oxide; Peroxidase; Ranitidine; Rats; Rats, Wistar; Stomach; Stomach Ulcer