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托吡酯通过抑制氧化应激对乙酸诱导的大鼠结肠炎的保护作用。

Protective effects of topiramate on acetic acid-induced colitis in rats through the inhibition of oxidative stress.

机构信息

Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran.

Department of Nutrition, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2024 Feb;397(2):1141-1149. doi: 10.1007/s00210-023-02677-1. Epub 2023 Aug 26.

Abstract

Ulcerative colitis is an intestinal inflammatory condition characterized by a rise in inflammatory mediator production and oxidative stress. Topiramate is an anticonvulsant agent with effectiveness on a wide range of seizures, which is anti-oxidative. This study aims to examine the protective effects of topiramate on acetic acid-induced ulcerative colitis in rats. Rats were randomly divided into four groups as follows: control, acetic acid, acetic acid + topiramate, and acetic acid + dexamethasone groups. Topiramate (100 mg/kg/day) or dexamethasone (2 mg/kg/day) was administered for six consecutive days, and ulcerative colitis was induced on the first day of the study by transrectal administration of 4% acetic acid. Four hours after the last dose of treatments, animals of each group were sacrificed, and colon tissues were removed for further macroscopic, histopathologic, and biochemical analyses. Treatment with topiramate markedly decreased colonic lesions and macroscopic scores as well as the improvement of histopathologic changes. Topiramate also effectively decreased the levels of malondialdehyde and upregulated the activity of anti-oxidative enzymes, including catalase, superoxide dismutase, and glutathione peroxidase. Our results reveal that the administration of topiramate ameliorates acetic acid-induced colitis in rats via anti-oxidative properties, and further studies may introduce it as an effective therapeutic candidate to decrease ulcerative colitis severity.

摘要

溃疡性结肠炎是一种肠道炎症性疾病,其特征是炎症介质产生和氧化应激增加。托吡酯是一种具有广泛抗癫痫作用的抗惊厥药物,具有抗氧化作用。本研究旨在探讨托吡酯对乙酸诱导的大鼠溃疡性结肠炎的保护作用。大鼠随机分为四组:对照组、乙酸组、乙酸+托吡酯组和乙酸+地塞米松组。托吡酯(100mg/kg/天)或地塞米松(2mg/kg/天)连续给药 6 天,在研究的第一天通过直肠给予 4%乙酸诱导溃疡性结肠炎。最后一次治疗后 4 小时,每组动物处死,取出结肠组织进行进一步的宏观、组织病理学和生化分析。托吡酯治疗明显减轻了结肠病变和宏观评分,以及组织病理学改变的改善。托吡酯还能有效降低丙二醛水平,并上调抗氧化酶的活性,包括过氧化氢酶、超氧化物歧化酶和谷胱甘肽过氧化物酶。我们的结果表明,托吡酯通过抗氧化作用改善了乙酸诱导的大鼠结肠炎,进一步的研究可能会将其作为一种有效的治疗候选药物来减轻溃疡性结肠炎的严重程度。

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