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A protective effect of the synthetic coumarine derivative Cloricromene against DNB-colitis in the rat

机译：合成香豆素衍生物Cloricromene对DNB结肠炎的保护作用

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Biologic therapies, namely antibodies against tumor necrosis factor-alpha (TNF-alpha) or its receptors, have been recently introduced for the treatment of patients with inflammatory bowel disease (IBD). In the present study the effects of cloricromene, an agent with known antithrombotic actions and with demonstrated anti-TNF-alpha activity were investigated in a rat model of experimental colitis induced with dinitrobenzenesulphonic acid (DNB)/ethanol. We investigated three experimental groups: (i) sham-colitis with vehicle-treatment (controls, n = 6), (ii) colitis with vehicle-treatment (saline, 0.1 ml s.c., daily) (DNB-V, n = 7), (iii) colitis with cloricromene-treatment (10 mg/ kg/day s.c.; DNB-C, n = 8). After 7 days, the weight gain, colon wet weight, macroscopic damage score, coagulation parameters, colon mucosal myeloperoxidase activity (MPO), and tissue concentrations of TNF-alpha and of macrophage inhibitory peptide-2 (MIP-2) were assessed. The macroscopic damage scores, colon wet weights, and tissue MIP-2 levels were significantly increased in untreated and in cloricromene-treated rats compared with controls. Cloricromene treatment was associated with a minor body weight loss (p < 0.025) and significantly reduced tissue concentrations of MPO and TNF-alpha (p < 0.02, both). Blood coagulation parameters were not affected by treatment. In the DNB-model treatment with cloricromene effectively reduces tissue levels of TNF-alpha and of myeloperoxidase, whereas MIP-2 concentrations were not influenced. Blood coagulation parameters remained unchanged indicating safety of treatment. Since biological therapies frequently fail to improve disease course of IBD, other therapies with similar targets should be further investigated. (C) 2004 Elsevier Inc. All rights reserved. [References: 36]
机译：最近已经引入了生物疗法，即针对肿瘤坏死因子-α（TNF-α）或其受体的抗体，用于治疗炎性肠病（IBD）患者。在本研究中，在由二硝基苯磺酸（DNB）/乙醇诱导的实验性结肠炎的大鼠模型中，研究了具有已知抗血栓作用和已证明具有抗TNF-α活性的clocloromene的作用。我们调查了三个实验组：（i）假手术治疗假性结肠炎（对照组，n = 6），（ii）假手术治疗结肠炎（生理盐水，每天0.1 ml sc）（DNB-V，n = 7） ，（iii）氯吡甲隆治疗结肠炎（10 mg / kg /天sc; DNB-C，n = 8）。 7天后，评估体重增加，结肠湿重，宏观损伤评分，凝血参数，结肠粘膜髓过氧化物酶活性（MPO）以及TNF-α和巨噬细胞抑制肽2（MIP-2）的组织浓度。与对照组相比，未经处理和经氯丁烯处理的大鼠的宏观损伤评分，结肠湿重和组织MIP-2水平显着增加。 Clocloromene治疗与轻微的体重减轻（p <0.025）和MPO和TNF-α的组织浓度显着降低（p <0.02，两者）有关。凝血参数不受治疗的影响。在DNB模型中，用次生环烯有效治疗可有效降低TNF-α和髓过氧化物酶的组织水平，而MIP-2的浓度不受影响。凝血参数保持不变，表明治疗的安全性。由于生物疗法常常不能改善IBD的病程，因此应进一步研究具有相似靶标的其他疗法。 （C）2004 Elsevier Inc.保留所有权利。 [参考：36]

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