Mahdy Raghda N El, Nader Manar A, Helal Manar G, Abu-Risha Sally E, Abdelmageed Marwa E
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
Department of Pharmacy Practice, Faculty of Pharmacy, Sinai University- Kantra Branch, Ismailia, Egypt.
Naunyn Schmiedebergs Arch Pharmacol. 2025 May;398(5):5611-5628. doi: 10.1007/s00210-024-03631-5. Epub 2024 Nov 23.
A chronic inflammatory condition of the colon called ulcerative colitis (UC) is characterized by mucosal surface irritation that extends from the rectum to the near proximal colon portions. The rationale of this work was to conclude if dulaglutide (Dula) could protect rats from developing colitis caused by exposure to acetic acid (AA). Rats were randomly divided into seven groups (each with eight rats): Normal control, Dula control, AA (received 2 milliliters of 3% v/v AA through the rectum), Sulfasalazine (SLZ); given SLZ (100 mg/kg) orally from day 11 to day 21 then AA intrarectally on day 22 and Dula groups ( pretreated with 50, 100 or 150 μg/kg subcutaneous injection of Dula - once weekly for three weeks and AA on day 22 to induce ulcerative colitis, colon tissues and blood samples were taken on day 23. By generating colonic histological deviations such as inflammatory processes, goblet cell death, glandular hyperplasia, and mucosa ulcers, Dula dropped AA-induced colitis. Additionally, these modifications diminished blood lactate dehydrogenase (LDH), C-reactive protein (CRP), colon weight, and the weight/length ratio of the colon. In addition, Dula decreased the oxidative stress biomarker malondialdehyde (MDA) and increased the antioxidant enzymes (total antioxidant capacity (TAC), reduced glutathione (GSH), and superoxide dismutase (SOD) concentrations). Dula also significantly reduced the expression of transforming growth factor-1 (TGF-β1), phosphatidylinositol-3-kinase (PI3K), protein kinase B (AKT) signaling pathway, and the inflammatory cytokines: nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), and interferon-γ (IFN-γ) in colonic cellular structures. In addition, Dula enforced the levels of glucagon-like peptide-1 (GLP-1) and trefoil factor-3 (TFF-3) that were crucial to intestinal mucosa regeneration and healing of wounds. By modulating TGF-β1 in conjunction with other inflammatory pathways like PI3K/AKT and NF-κB, regulating the oxidant/antioxidant balance, and improving the integrity of the intestinal barrier, Dula prevented AA-induced colitis in rats.
一种称为溃疡性结肠炎（UC）的结肠慢性炎症性疾病，其特征是黏膜表面受到刺激，范围从直肠延伸至近端结肠的近段部分。这项研究的目的是确定度拉糖肽（Dula）是否能保护大鼠免受因接触乙酸（AA）而引发的结肠炎。大鼠被随机分为七组（每组八只）：正常对照组、Dula对照组、AA组（通过直肠给予2毫升3% v/v的AA）、柳氮磺胺吡啶（SLZ）组；从第11天至第21天口服给予SLZ（100毫克/千克），然后在第22天经直肠给予AA，以及Dula组（分别用50、100或150微克/千克皮下注射Dula进行预处理 - 每周一次，共三周，在第22天给予AA以诱导溃疡性结肠炎，在第23天采集结肠组织和血液样本。通过产生结肠组织学偏差，如炎症过程、杯状细胞死亡、腺体增生和黏膜溃疡，Dula减轻了AA诱导的结肠炎。此外，这些改变降低了血乳酸脱氢酶（LDH）、C反应蛋白（CRP）、结肠重量以及结肠重量/长度比。此外，Dula降低了氧化应激生物标志物丙二醛（MDA），并提高了抗氧化酶（总抗氧化能力（TAC）、还原型谷胱甘肽（GSH）和超氧化物歧化酶（SOD））的浓度。Dula还显著降低了结肠细胞结构中转化生长因子-1（TGF-β1）、磷脂酰肌醇-3-激酶（PI3K）、蛋白激酶B（AKT）信号通路以及炎症细胞因子：核因子κB（NF-κB）、白细胞介素-6（IL-6）和干扰素-γ（IFN-γ）的表达。此外，Dula提高了对肠黏膜再生和伤口愈合至关重要的胰高血糖素样肽-1（GLP-1）和三叶因子-3（TFF-3）的水平。通过调节TGF-β1以及其他炎症途径，如PI3K/AKT和NF-κB，调节氧化/抗氧化平衡，并改善肠道屏障的完整性，Dula预防了大鼠AA诱导的结肠炎。
