Marchi Patrícia, Paiotti Ana Paula Ribeiro, Artigiani Neto Ricardo, Oshima Celina Tizuko Fujiyama, Ribeiro Daniel Araki
Department of Pathology, Universidade Federal de São Paulo - Escola Paulista de Medicina, UNIFESP, SP, Brazil.
Department of Pathology, Universidade Federal de São Paulo - Escola Paulista de Medicina, UNIFESP, SP, Brazil; Department of Biosciences, Universidade Federal de São Paulo, UNIFESP, Santos, SP, Brazil.
Environ Toxicol Pharmacol. 2014 Mar;37(2):819-27. doi: 10.1016/j.etap.2014.02.006. Epub 2014 Feb 26.
Inflammatory bowel disease (IBD) is a common chronic gastrointestinal disorder characterized by alternating periods of remission and active intestinal inflammation. Flavonoids exert several biological activities, which are mainly related to their ability to inhibit inflammatory process and/or to their antioxidant properties, and are able to regulate the immune response. The aim of this study was to evaluate whether phenolic compounds present in grape juice could reduce the inflammatory effects induced by experimental colitis. A total of 41 male Wistar rats were randomized into seven groups, as follows: G1--Sham group: sham induced-colitis rats; G2--(2,4,6-rinitrobenzenesulfonic acid) TNBS group: nontreated induced-colitis; G3--2% grape juice control group; G4--1% grape juice 24h after TNBS colitis induction; G5--1% grape juice on day 7 after colitis induction; G6--2% grape juice 24h after colitis induction; G7--2% grape juice on day 7 after colitis induction. Genotoxicity was evaluated by comet assay. Immunohistochemistry was determined using the streptavidin-biotin-peroxidase method being analyzed in control (normal tissue) and "hot spot" areas i.e., presenting inflammatory process being graded as 1 (weak), 2 (moderate), or 3 (strong). Both parameters were evaluated in the cytoplasm of epithelial or inflammatory cells. TNF-immunoexpression and iNOS were reduced after drinking grape juice 24 h or after 7 days for all doses tested. COX-2 was reduced in the groups exposed to 1% grape juice 24 h or 7 days of exposure. The grape juice at 1% dose in the last 7 days of treatment as well as grape juice at 2% dose decreased the peripheral blood genotoxicity. Taken together, the grape juice mainly at 1% dose exerts anti-inflammatory effects in chronic colitis caused by TNBS as a result of down regulation in the expression of pro-inflammatory cytokines and reduction of genotoxicity in peripheral blood cells.
炎症性肠病（IBD）是一种常见的慢性胃肠道疾病，其特征是缓解期和肠道炎症活跃期交替出现。类黄酮具有多种生物活性，主要与其抑制炎症过程的能力和/或抗氧化特性有关，并且能够调节免疫反应。本研究的目的是评估葡萄汁中存在的酚类化合物是否可以减轻实验性结肠炎诱导的炎症作用。总共41只雄性Wistar大鼠被随机分为七组，如下：G1——假手术组：假手术诱导的结肠炎大鼠；G2——（2,4,6-三硝基苯磺酸）TNBS组：未治疗的诱导性结肠炎；G3——2%葡萄汁对照组；G4——TNBS诱导结肠炎后24小时给予1%葡萄汁；G5——结肠炎诱导后第7天给予1%葡萄汁；G6——结肠炎诱导后24小时给予2%葡萄汁；G7——结肠炎诱导后第7天给予2%葡萄汁。通过彗星试验评估遗传毒性。使用链霉亲和素-生物素-过氧化物酶方法进行免疫组织化学测定，并在对照（正常组织）和“热点”区域进行分析，即呈现炎症过程的区域，炎症程度分为1级（弱）、2级（中度）或3级（强）。两个参数均在上皮细胞或炎症细胞的细胞质中进行评估。对于所有测试剂量，饮用葡萄汁24小时或7天后，TNF免疫表达和诱导型一氧化氮合酶（iNOS）均降低。在暴露于1%葡萄汁24小时或7天的组中，环氧合酶-2（COX-2）降低。在治疗的最后7天给予1%剂量的葡萄汁以及2%剂量的葡萄汁可降低外周血遗传毒性。综上所述，主要是1%剂量的葡萄汁通过下调促炎细胞因子的表达和降低外周血细胞的遗传毒性，对TNBS引起的慢性结肠炎发挥抗炎作用。
