Journal
EXPERT OPINION ON THERAPEUTIC TARGETS
Volume 26, Issue 5, Pages 487-506Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/14728222.2022.2077723
Keywords
Asthma; dapagliflozin; interleukin-17; nitric oxide; soluble guanylyl cyclase; cyclic GMP; S100 calcium-binding protein A4
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This study investigated the potential therapeutic effects of Dapagliflozin on lung inflammation, oxidative stress, and bronchospasm in a rat asthma model. The results showed that Dapagliflozin has anti-inflammatory, antioxidant, and bronchodilator properties, making it a promising option for future asthma treatment.
Background 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. Research design and methods 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, TNF alpha, IL-1 beta, 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. Results DAPA significantly reduced (p ) airway inflammatory-oxidative markers (IL-17, TNF alpha, IL-1 beta, MCP1, and MDA), but increased (p ) TAC, and mitigated bronchospasm by activating NO/sGC/cGMP and reducing S100A4 (p ). The biochemical and western blot studies were supported by histopathological and immunohistochemical investigations. Conclusions 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.
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