Novel effects of ectoine, a bacteria-derived natural tetrahydropyrimidine, in experimental colitis
Novel effects of ectoine, a bacteria-derived natural tetrahydropyrimidine, in experimental colitis
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DOI：
10.1016/j.phymed.2013.01.009
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发表时间：
2013-05-15
期刊：
影响因子：
7.9
通讯作者：
Khayyal, Mohamed T.
中科院分区：
文献类型：
--
作者：
Abdel-Aziz, Heba;Wadie, Walaa;Khayyal, Mohamed T.
有证据表明，肠屏障功能障碍在炎症性肠病(IBD)的病因中起着重要作用。因此，稳定粘膜屏障功能构成了一种新的治疗方法。Ectoine是好氧化学异养和嗜盐/耐盐细菌产生的一种相容的溶质，它作为渗透保护剂和有效的生物膜稳定剂，保护生产细胞免受极端环境胁迫的影响。由于这种天然化合物也被证明可以防止与IBD相关的炎症反应，因此在结肠炎模型中研究了它的潜在用途。各组大鼠每天口服不同剂量的ectoine(30-300 mg/kg)或柳氮磺胺吡啶(参照药)，为期11天。在第8天，当在接下来的3天内出现明显的病变体征时，通过结肠内滴注2，4，6-三硝基苯磺酸诱导结肠炎。第12天，从大鼠眶后神经丛抽血，处死动物。切除结肠，进行大体和显微检查。检测血清和结肠匀浆中氧化应激和炎症的相关参数。结肠炎的诱导导致体重显著减轻，结肠组织发生显著的病理变化，髓过氧化物酶、还原型谷胱甘肽、丙二醛和所有炎症标志物的水平发生变化。埃托品治疗可减轻TNBS诱导的结肠炎的炎性改变。这种作用与降低血清中的肿瘤坏死因子-α、白介素1-β、细胞间黏附分子-1、前列腺素E(2)和白三烯B4水平有关。(C)2013年爱思唯尔股份有限公司。版权所有。
Evidence suggests an important role of intestinal barrier dysfunction in the etiology of inflammatory bowel disease (IBD). Therefore stabilizing mucosal barrier function constitutes a new therapeutic approach in its management.Ectoine is a compatible solute produced by aerobic chemoheterotrophic and halophilic/halotolerant bacteria, where it acts as osmoprotectant and effective biomembrane stabilizer, protecting the producing cells from extreme environmental stress. Since this natural compound was also shown to prevent inflammatory responses associated with IBD, its potential usefulness was studied in a model of colitis.Groups of rats were treated orally with different doses of ectoine (30-300 mg/kg) or sulfasalazine (reference drug) daily for 11 days. On day 8 colitis was induced by intracolonic instillation of 2,4,6-trinitrobenzenesulfonic acid, when overt signs of lesions develop within the next 3 days. On day 12, blood was withdrawn from the retro-orbital plexus of the rats and the animals were sacrificed. The colon was excised and examined macroscopically and microscopically. Relevant parameters of oxidative stress and inflammation were measured in serum and colon homogenates.Induction of colitis led to marked weight loss, significant histopathological changes of the colon, and variable changes in levels of myeloperoxidase, reduced glutathione, malondialdehyde, and all inflammatory markers tested. Treatment with ectoine ameliorated the inflammatory changes in TNBS-induced colitis. This effect was associated with reduction in the levels of TNF-alpha, IL-1 beta, ICAM-1, PGE(2) and LTB4.The findings suggest that intestinal barrier stabilizers from natural sources could offer new therapeutic measures for the management of IBD. (c) 2013 Elsevier GmbH. All rights reserved.