Kammeyer Arthur, Peters Charlotte P, Meijer Sybren L, Te Velde Anje A
Department of Dermatology, Academic Medical Center (AMC), University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands.
ISRN Inflamm. 2012 Sep 5;2012:898153. doi: 10.5402/2012/898153. eCollection 2012.
Urocanic acid (UCA) derivatives were tested for their anti-inflammatory activity in inflammatory bowel disease (IBD) in two models: ex vivo and an experimental mouse model. Ex vivo: inflamed colonic tissue was incubated in culture medium with or without the UCA derivatives. Biopsies, incubated with UCA derivatives, produced lower levels of proinflammatory cytokines IL-6 and IL-8 as compared to control biopsies. The same compounds also showed increased levels of IL-10, providing an additional indication for anti-inflammatory properties. In vivo: a combination of two imidazoles and a combination of two of their ethyl esters were administered to mice while colitis was induced by oral administration of dextran sodium sulfate (DSS). Some parameters did not show conclusive effects, but the imidazoles and their ethyl esters reduced the area of inflammation and the number of infiltrating neutrophils. Fibrosis and the sum of all histological aspects were reduced by the imidazoles, whereas the ethyl esters reduced the colon weight to length ratio. These results suggest that the UCA derivatives have anti-inflammatory effect on IBD. In addition, fine tuning of the ex vivo model may provide an elegant way to predict anti-inflammatory effects of potential drugs in humans, which may decrease the need for animal experiments.
在两种模型中测试了尿刊酸（UCA）衍生物在炎症性肠病（IBD）中的抗炎活性：体外模型和实验性小鼠模型。体外模型：将发炎的结肠组织在含有或不含有UCA衍生物的培养基中孵育。与对照活检相比，用UCA衍生物孵育的活检产生的促炎细胞因子IL-6和IL-8水平较低。相同的化合物还显示IL-10水平升高，为抗炎特性提供了额外的证据。体内模型：在通过口服给予葡聚糖硫酸钠（DSS）诱导小鼠结肠炎的同时，给小鼠施用两种咪唑的组合及其两种乙酯的组合。一些参数没有显示出确凿的效果，但咪唑及其乙酯减少了炎症面积和浸润中性粒细胞的数量。咪唑减少了纤维化和所有组织学方面的总和，而乙酯降低了结肠重量与长度的比率。这些结果表明，UCA衍生物对IBD具有抗炎作用。此外，体外模型的微调可能提供一种优雅的方法来预测潜在药物在人体中的抗炎作用，这可能会减少动物实验的需求。
