Pharmacology & Environmental Toxicology, Environmental Studies & Research Institute (ESRI), University of Sadat City, Sadat City, Egypt.
Environmental Studies & Research Institute (ESRI), University of Sadat City, Minofia Governorate, Egypt.
Expert Opin Ther Targets. 2022 May;26(5):487-506. doi: 10.1080/14728222.2022.2077723. Epub 2022 Jun 2.
Asthma is a chronic inflammatory lung disease that universally affects millions of people. Despite numerous well-defined medications, asthma is poorly managed. This study aims to clarify the potential therapeutic effect of Dapagliflozin (DAPA) against lung inflammation, oxidative stress, and associated bronchospasm in OVA-sensitized rat asthma model.
Twenty-five rats were allocated into (Control, Asthma, DEXA, DAPA, and DAPA+DEXA). All treatments were administered orally once a day for two weeks. The BALF levels of IL-17, TNFα, IL-1β, and MCP-1 were determined to assess airway inflammation. For oxidative stress determination, BALF MDA levels and TAC were measured. The BALF S100A4 level and NO/sGC/cGMP pathway were detected. Lung histopathological findings and immunohistochemical investigation of eNOS and iNOS activities were recorded.
DAPA significantly reduced () airway inflammatory-oxidative markers (IL-17, TNFα, IL-1β, MCP1, and MDA), but increased () TAC, and mitigated bronchospasm by activating NO/sGC/cGMP and reducing S100A4 (). The biochemical and western blot studies were supported by histopathological and immunohistochemical investigations.
DAPA presents a new prospective possibility for future asthma therapy due to its anti-inflammatory, anti-oxidant, and bronchodilator properties. DAPA has the property of reducing Dexamethasone (DEXA)-associated unfavorable effects during asthma treatment.
哮喘是一种慢性炎症性肺部疾病，普遍影响着数百万人。尽管有许多明确的药物，但哮喘的管理仍不理想。本研究旨在阐明达格列净（DAPA）对 OVA 致敏大鼠哮喘模型中肺部炎症、氧化应激和相关支气管痉挛的潜在治疗作用。
25 只大鼠被分为（对照组、哮喘组、DEXA 组、DAPA 组和 DAPA+DEXA 组）。所有治疗均每日口服一次，持续两周。通过测定 BALF 中 IL-17、TNFα、IL-1β 和 MCP-1 的水平来评估气道炎症。为了确定氧化应激，测定 BALF MDA 水平和 TAC。检测 BALF S100A4 水平和 NO/sGC/cGMP 通路。记录肺组织病理学发现和 eNOS 和 iNOS 活性的免疫组化研究。
DAPA 显著降低（）气道炎症-氧化标志物（IL-17、TNFα、IL-1β、MCP1 和 MDA），但增加（）TAC，并通过激活 NO/sGC/cGMP 和降低 S100A4（）来缓解支气管痉挛。生化和 Western blot 研究得到了组织病理学和免疫组化研究的支持。
由于具有抗炎、抗氧化和支气管扩张作用，DAPA 为未来的哮喘治疗提供了新的前景。DAPA 具有减轻哮喘治疗中地塞米松（DEXA）相关不良作用的特性。
