■肠道粘膜免疫细胞,特别是肥大细胞,在溃疡性结肠炎(UC)的病理生理学中至关重要。它的激活提高了组胺的组织浓度。抑制结肠组胺释放可能是治疗UC的有效治疗策略。2,4,6-三硝基苯磺酸(TNBS)诱导大鼠结肠炎的实验模型模拟人IBD,辅助治疗调查。药物再利用是探索已建立药物的新适应症的有希望的策略。地氯雷他定(DES)是第二代抗组胺药,用于通过阻断体内组胺的作用来控制过敏。它还报道了抗炎和抗氧化作用。
■通过TNBS诱导的Wistar大鼠结肠炎的临床前筛查,研究了DES在UC中的再利用潜力。
■分别和与标准药物5-氨基水杨酸(5-ASA)联合使用评估了DES的疗效。大鼠口服DES(10mg/kg),5-ASA(25mg/kg),和DES+5-ASA(5mg+12.15mg)诱导结肠炎后。参数包括疾病活动评分率(DASR),结肠/体重比(CBWR),结肠长度,直径,pH值,组织学损伤,并进行评分评价。炎症生物标志物如IL-1β,TNF-α,连同还原型谷胱甘肽(GSH),和丙二醛(MDA)进行评估。
■DES的显著保护作用,特别是与5-ASA结合,观察到针对TNBS诱导的炎症的DASR降低,CBWR,改善结肠形态。药物显着降低血浆和结肠组胺,细胞因子水平。GSH恢复,并观察到MDA含量降低。
■DES和DES+5-ASA在减轻与TNBS诱导的大鼠结肠炎相关的结肠炎症中显示出潜力。这种作用可以归因于其抗组胺药,抗细胞因子,和抗氧化性能。
UNASSIGNED: Intestinal mucosal immune cells, notably mast cells, are pivotal in ulcerative colitis (UC) pathophysiology. Its activation elevates tissue concentrations of histamine. Inhibiting colonic histamine release could be an effective therapeutic strategy for treating UC. Experimental model like 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats mimic human IBD, aiding treatment investigations. Drug repurposing is a promising strategy to explore new indications for established drugs. Desloratadine (DES) is second-generation antihistamine utilized for managing allergies by blocking histamine action in the body. It also has reported anti-inflammatory and antioxidant actions.
UNASSIGNED: DES was investigated for its repurposing potential in UC by preclinical screening in TNBS-induced colitis in Wistar rats.
UNASSIGNED: Therapeutic efficacy of DES was evaluated both individually and in combination with standard drug 5-aminosalicylicacid (5-ASA). Rats were orally administered DES (10 mg/kg), 5-ASA (25 mg/kg), and DES + 5-ASA (5 mg + 12.15 mg) following the induction of colitis. Parameters including disease activity score rate (DASR), colon/body weight ratio (CBWR), colon length, diameter, pH, histological injury, and scoring were evaluated. Inflammatory biomarkers such as IL-1β, TNF-α, along with reduced glutathione (GSH), and malondialdehyde (MDA) were assessed.
UNASSIGNED: Significant protective effects of DES, especially in combination with 5-ASA, against TNBS-induced inflammation were observed as evidenced by reduced DASR, CBWR, and improved colon morphology. Drugs significantly lowered plasma and colon histamine and, cytokines levels. GSH restoration, and decreased MDA content were also observed.
UNASSIGNED: DES and DES + 5-ASA demonstrated potential in alleviating colonic inflammation associated with TNBS-induced colitis in rats. The effect can be attributed to its antihistamine, anticytokine, and antioxidative properties.