Antiulcer activity of fluvoxamine in rats and its effect on oxidant and antioxidant parameters in stomach tissue.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Dursun
Hakan
H
Department of Pharmacology, Ataturk University, Faculty of Medicine, Erzurum, Turkey. hadursun@hotmail.com
Bilici
Mehmet
M
Albayrak
Fatih
F
Ozturk
Cengiz
C
Saglam
Mustafa B
MB
Alp
Hamit H
HH
Suleyman
Halis
H
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016666:Fluvoxamine / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D007213:Indomethacin / Q000009:adverse effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism*; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects; D013276:Stomach Ulcer / Q000139:chemically induced / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D009569:Nitric Oxide; D008315:Malondialdehyde; D011899:Ranitidine; D009195:Peroxidase; D005978:Glutathione; D016666:Fluvoxamine; D007213:Indomethacin