氟伏沙明在大鼠中的抗溃疡活性及其对胃组织氧化和抗氧化参数的影响。

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

作者信息

Dursun Hakan, Bilici Mehmet, Albayrak Fatih, Ozturk Cengiz, Saglam Mustafa B, Alp Hamit H, Suleyman Halis

机构信息

Department of Pharmacology, Ataturk University, Faculty of Medicine, Erzurum, Turkey.

出版信息

BMC Gastroenterol. 2009 May 20;9:36. doi: 10.1186/1471-230X-9-36.

DOI:10.1186/1471-230X-9-36

PMID:19457229

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2693117/

Abstract

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.

CONCLUSION

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.

摘要

背景

尽管有多种药物可用于治疗胃溃疡，但这些药物往往无效。许多抗抑郁药物在各种实验性溃疡模型中已显示出抗溃疡活性。其中一种药物，抗抑郁药米氮平，据报道其抗溃疡作用涉及抗氧化参数增加和氧化参数降低。然而，迄今为止，尚无关于类似抗抑郁药氟伏沙明抗溃疡活性的信息。本研究旨在探讨氟伏沙明的抗溃疡作用，并确定其与抗氧化剂的关系。

方法

将禁食24小时的大鼠分组，通过口服灌胃给予氟伏沙明（25、50、100和200毫克/千克）、雷尼替丁（50毫克/千克）或蒸馏水。给大鼠口服吲哚美辛（25毫克/千克）作为溃疡诱导剂。诱导溃疡6小时后，切除大鼠的胃并测定溃疡指数。用相同剂量的氟伏沙明和雷尼替丁对另一组大鼠进行治疗，但不给予吲哚美辛，以测试这些药物单独对生化参数的影响。对胃进行生化评估以确定氧化和抗氧化参数。我们使用单因素方差分析和最小显著差异（LSD）选项进行数据分析。

结果

与对照大鼠组相比，25、50、100和200毫克/千克剂量的氟伏沙明的抗溃疡作用分别为48.5%、67.5%、82.1%和96.1%。雷尼替丁显示出86.5%的抗溃疡作用。在未用吲哚美辛治疗的情况下，任何剂量的氟伏沙明或雷尼替丁均未观察到差异。与仅用吲哚美辛组相比，所有氟伏沙明组和雷尼替丁组的抗氧化参数、总谷胱甘肽和一氧化氮水平均升高。此外，与吲哚美辛组相比，氟伏沙明和雷尼替丁降低了大鼠胃组织中氧化参数、髓过氧化物酶和丙二醛的水平。