Desloratadine via its anti-inflammatory and antioxidative properties ameliorates TNBS-induced experimental colitis in rats.

IF 2.9 4区医学 Q3 IMMUNOLOGY

Immunopharmacology and Immunotoxicology Pub Date : 2024-08-01 Epub Date: 2024-05-30 DOI:10.1080/08923973.2024.2360043

Mohammad Aadil Bhat, Supriya Roy, Suneela Dhaneshwar, Swatantra Kumar, Shailendra K Saxena

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引用次数: 0

Abstract

Background: 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.

Objective: DES was investigated for its repurposing potential in UC by preclinical screening in TNBS-induced colitis in Wistar rats.

Methods: 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.

Results: 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.

Conclusion: 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.

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地氯雷他定具有抗炎和抗氧化作用，可改善 TNBS 引起的大鼠实验性结肠炎。

背景：肠粘膜免疫细胞，尤其是肥大细胞，是溃疡性结肠炎（UC）病理生理学的关键。肥大细胞的活化会提高组织中组胺的浓度。抑制结肠组胺释放可能是治疗溃疡性结肠炎的有效治疗策略。2,4,6-三硝基苯磺酸（TNBS）诱导的大鼠结肠炎等实验模型与人类 IBD 相似，有助于治疗研究。药物再利用是为既有药物探索新适应症的一种有前途的策略。地氯雷他定（DES）是第二代抗组胺药，通过阻断组胺在体内的作用来控制过敏。据报道，它还具有抗炎和抗氧化作用：通过在 TNBS 诱导的 Wistar 大鼠结肠炎中进行临床前筛选，研究 DES 在 UC 中的再利用潜力：方法：对DES单独使用以及与标准药物5-氨基水杨酸（5-ASA）联合使用的疗效进行评估。大鼠在诱导结肠炎后分别口服 DES（10 毫克/千克）、5-ASA（25 毫克/千克）和 DES + 5-ASA（5 毫克 + 12.15 毫克）。评估的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、组织学损伤和评分。对 IL-1β、TNF-α 等炎症生物标志物以及还原型谷胱甘肽（GSH）和丙二醛（MDA）进行了评估：结果：DES（尤其是与 5-ASA 联用）对 TNBS 诱导的炎症有显著的保护作用，这体现在 DASR、CBWR 的降低和结肠形态的改善上。药物明显降低了血浆和结肠中组胺及细胞因子的水平。还观察到 GSH 恢复和 MDA 含量降低：结论：DES 和 DES + 5-ASA 有助于缓解 TNBS 引起的大鼠结肠炎。该效果可归因于其抗组胺、抗细胞因子和抗氧化特性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Immunopharmacology and Immunotoxicology 医学-毒理学

CiteScore

5.40

自引率

0.00%

发文量

133

审稿时长

4-8 weeks

期刊介绍： The journal Immunopharmacology and Immunotoxicology is devoted to pre-clinical and clinical drug discovery and development targeting the immune system. Research related to the immunoregulatory effects of various compounds, including small-molecule drugs and biologics, on immunocompetent cells and immune responses, as well as the immunotoxicity exerted by xenobiotics and drugs. Only research that describe the mechanisms of specific compounds (not extracts) is of interest to the journal. The journal will prioritise preclinical and clinical studies on immunotherapy of disorders such as chronic inflammation, allergy, autoimmunity, cancer etc. The effects of small-drugs, vaccines and biologics against central immunological targets as well as cell-based therapy, including dendritic cell therapy, T cell adoptive transfer and stem cell therapy, are topics of particular interest. Publications pointing towards potential new drug targets within the immune system or novel technology for immunopharmacological drug development are also welcome. With an immunoscience focus on drug development, immunotherapy and toxicology, the journal will cover areas such as infection, allergy, inflammation, tumor immunology, degenerative disorders, immunodeficiencies, neurology, atherosclerosis and more. Immunopharmacology and Immunotoxicology will accept original manuscripts, brief communications, commentaries, mini-reviews, reviews, clinical trials and clinical cases, on the condition that the results reported are based on original, clinical, or basic research that has not been published elsewhere in any journal in any language (except in abstract form relating to paper communicated to scientific meetings and symposiums).