Evaluating the antioxidant potential of new treatments for inflammatory bowel disease using a rat model of colitis
Evaluating the antioxidant potential of new treatments for inflammatory bowel disease using a rat model of colitis
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DOI：
10.1136/gut.39.3.407
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发表时间：
1996-09-01
期刊：
影响因子：
24.5
通讯作者：
Blake, DR
中科院分区：
文献类型：
--
作者：
Millar, AD;Rampton, DS;Blake, DR
活性氧可能介导炎症性肠病的组织损伤。氨基水杨酸酯具有抗氧化活性，抗氧化剂超氧化物歧化酶和别嘌呤醇，目的是开发一种方便的技术，用于测试用于炎症性肠病的标准和新型治疗剂的抗氧化潜力。方法-用放大化学发光法测定乙酸诱导的结肠炎大鼠结肠标本中反应性物质的产生，并评估其在结肠炎中的作用。传统抗氧化剂、标准疗法和提出的炎症性肠病新疗法的体外效应。结果-通过证明传统抗氧化剂对乙酸诱导的结肠炎活检标本的化学发光的影响概况，（叠氮化钠，过氧化氢酶，铜锌超氧化物歧化酶，二甲基亚砜，N-乙酰半胱氨酸和抗坏血酸）和标准疗法（5-氨基水杨酸和氢化可的松）类似于先前使用溃疡性结肠炎活检标本报道的结果。人重组锰超氧化物歧化酶没有改变化学发光。两种新化合物LY 231617（10 mM）和安氟替唑（20 mM）可使化学发光降低98%（n=5，p=0.009）和88%（n=5，p=0.03），respectively.Conclusions-来自乙酸诱导的结肠炎和溃疡性结肠炎的结肠活检标本的化学发光响应与一系列常规抗氧化剂和标准治疗的相似性表明，该模型是用于测试炎性肠病的新疗法的抗氧化潜力的有用方法。二甲亚砜，抗坏血酸，和新的化合物，安氟替唑和LY 231617在这个模型中的抗氧化作用表明，这些药物值得进一步评估炎症性肠病的治疗。
Background-Reactive oxygen species may mediate tissue injury in inflammatory bowel disease. Aminosalicylates have antioxidant activity and the antioxidants, superoxide dismutase and allopurinol, are of reported benefit in inflammatory bowel disease.Aim-To develop a convenient technique for testing the antioxidant potential of standard and novel therapeutic agents for use in inflammatory bowel disease.Methods-Amplified chemiluminescence was used to measure reactive species production by colonic specimens from rats with acetic acid induced colitis and to assess the in vitro effect of conventional antioxidants, standard therapies and proposed novel therapies for inflammatory bowel disease.Results-The model was validated by demonstrating that the profile of effects on chemiluminescence of acetic acid induced colitis biopsy specimens given by conventional antioxidants (sodium azide, catalase, copper-zinc superoxide dismutase, dimethyl sulphoxide, N-acetylcysteine and ascorbate) and standard therapies (5-aminosalicylate and hydrocortisone) resembled that previously reported using biopsy specimens from ulcerative colitis. Human recombinant manganese superoxide dismutase did not alter chemiluminescence. Two novel compounds, LY231617 (10 mM) and amflutizole (20 mM), reduced chemiluminescence by 98% (n=5, p=0.009) and 88% (n=5, p=0.03), respectively.Conclusions-The similarity of the chemiluminescence responses of colonic biopsy specimens from acetic acid induced colitis and ulcerative colitis to a range of conventional antioxidants and standard treatments suggests that this model is a useful method for testing the antioxidant potential of new therapies for inflammatory bowel disease. The antioxidant actions of dimethyl sulphoxide, ascorbate, and the novel compounds, amflutizole and LY231617 in this model suggest that these agents merit further assessment in the treatment of inflammatory bowel disease.