Jung Eun Suk, Jang Hyun Joo, Hong Eun Mi, Lim Hye Li, Lee Sang Pyo, Kae Sea Hyub, Lee Jin
Division of Gastroenterology, Department of Internal Medicine, Dongtan Sacred Heart Hospital, Hallym University School of Medicine, Hwaseong-si, Gyeonggi-do 18450, Korea.
Medicina (Kaunas). 2020 Oct 1;56(10):515. doi: 10.3390/medicina56100515.
Non-steroidal anti-inflammatory drugs (NSAIDs) have been among the major causes of small intestinal injury in clinical practice. As such, the current study investigated the protective effect of 5-aminosalicylic acid (5-ASA) against an NSAID-induced small intestinal injury. : IEC-6 cells were treated with various concentrations of indomethacin with or without 5-ASA in a serum-free medium, after which an 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Dromide (MTT) assay, a cell apoptosis assay, a caspase-3 activity assay, a reactive oxygen species (ROS) content and Superoxide dismutase 2 (SOD2) activity measurement, a Western blotting for occludin and zonula occludens-1 (ZO-1) and a wound healing assay were conducted. 5-ASA ameliorated indomethacin-induced cell apoptosis and an increase in the intracellular ROS content while augmenting the indomethacin-induced suppression of SOD2 activity in IEC-6 cells. Moreover, 5-ASA reversed the indomethacin-induced attenuation of occludin and ZO-1 expression and promoted faster wound healing effects in IEC-6 cells following an indomethacin-induced injury. Our results suggested that 5-ASA protects small intestinal cells against an NSAID-induced small intestinal injury by scavenging free radicals. Therefore, 5-ASA could be a potential treatment for an NSAID-induced small intestinal injury.
非甾体抗炎药(NSAIDs)一直是临床实践中导致小肠损伤的主要原因之一。因此,本研究调查了5-氨基水杨酸(5-ASA)对NSAID诱导的小肠损伤的保护作用。在无血清培养基中,用不同浓度的吲哚美辛处理IEC-6细胞,同时加入或不加入5-ASA,之后进行3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)检测、细胞凋亡检测、半胱天冬酶-3活性检测、活性氧(ROS)含量和超氧化物歧化酶2(SOD2)活性测定、紧密连接蛋白和闭合蛋白-1(ZO-1)的蛋白质印迹分析以及伤口愈合检测。5-ASA改善了吲哚美辛诱导的细胞凋亡和细胞内ROS含量的增加,同时增强了吲哚美辛诱导的IEC-6细胞中SOD2活性的抑制。此外,5-ASA逆转了吲哚美辛诱导的紧密连接蛋白和ZO-1表达的减弱,并在吲哚美辛诱导损伤后的IEC-6细胞中促进了更快的伤口愈合效果。我们的结果表明,5-ASA通过清除自由基保护小肠细胞免受NSAID诱导的小肠损伤。因此,5-ASA可能是治疗NSAID诱导的小肠损伤的一种潜在药物。