Klitgaard Mette, Kristensen Maja Nørgaard, Venkatasubramanian Ramakrishnan, Guerra Priscila, Jacobsen Jette, Berthelsen Ragna, Rades Thomas, Müllertz Anette
Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark.
The Danish National Research Foundation and Villum Foundation's Center for Intelligent Drug Delivery and Sensing Using Microcontainers and Nanomechanics (IDUN), Department of Health Technology, Technical University of Denmark, 2800, Kongens Lyngby, Denmark.
Drug Deliv Transl Res. 2023 May;13(5):1484-1499. doi: 10.1007/s13346-023-01313-y. Epub 2023 Mar 13.
Dextran sulfate sodium (DSS) is commonly used to induce colitis in rats. While the DSS-induced colitis rat model can be used to test new oral drug formulations for the treatment of inflammatory bowel disease, the effect of the DSS treatment on the gastrointestinal tract has not been thoroughly characterized. Additionally, the use of different markers to assess and confirm successful induction of colitis is somewhat inconsistent. This study aimed to investigate the DSS model to improve the preclinical evaluation of new oral drug formulations. The induction of colitis was evaluated based on the disease activity index (DAI) score, colon length, histological tissue evaluation, spleen weight, plasma C-reactive protein, and plasma lipocalin-2. Furthermore, the study investigated how the DSS-induced colitis affected the luminal pH, lipase activity, and concentrations of bile salts, polar lipids, and neutral lipids. For all evaluated parameters, healthy rats were used as a reference. The DAI score, colon length, and histological evaluation of the colon were effective disease indicators in DSS-induced colitis rats, while spleen weight, plasma C-reactive protein, and plasma lipocalin-2 were not. The luminal pH of the colon and bile salt- and neutral lipid concentrations in regions of the small intestine were lower in DSS-induced rats compared to healthy rats. Overall, the colitis model was deemed relevant for investigating ulcerative colitis-specific formulations.
硫酸葡聚糖钠(DSS)常用于诱导大鼠结肠炎。虽然DSS诱导的结肠炎大鼠模型可用于测试治疗炎症性肠病的新型口服药物制剂,但DSS治疗对胃肠道的影响尚未得到充分表征。此外,使用不同的标志物来评估和确认结肠炎的成功诱导在一定程度上并不一致。本研究旨在研究DSS模型,以改进新型口服药物制剂的临床前评估。基于疾病活动指数(DAI)评分、结肠长度、组织学组织评估、脾脏重量、血浆C反应蛋白和血浆脂质运载蛋白-2来评估结肠炎的诱导情况。此外,该研究还调查了DSS诱导的结肠炎如何影响肠腔pH值、脂肪酶活性以及胆汁盐、极性脂质和中性脂质的浓度。对于所有评估参数,均以健康大鼠作为对照。DAI评分、结肠长度和结肠组织学评估是DSS诱导的结肠炎大鼠有效的疾病指标,而脾脏重量、血浆C反应蛋白和血浆脂质运载蛋白-2则不是。与健康大鼠相比,DSS诱导的大鼠结肠肠腔pH值以及小肠区域的胆汁盐和中性脂质浓度较低。总体而言,该结肠炎模型被认为与研究溃疡性结肠炎特异性制剂相关。