Targeting the adenosinergic signaling pathway in the inflammatory response in rat lung tissue during moderate and severe chronic hypoxia

Authors : Özge Göktepe, Kemal Erdem Başaran, Pınar Alişan Suna, Demet Bolat, Arzu Yay

Pages : 22-37

Doi:10.17826/cumj.1525573

View : 212 | Download : 290

Publication Date : 2025-03-31

Article Type : Research Paper

Abstract :Purpose: Hypoxia occurs after inflammatory diseases in tissues and is associated with the induction of proinflammatory responses in addition to the breakdown of barriers. Adenosine receptors are critical in the initiation and regulation of this response. The effectiveness of externally applied adenosine receptor agonists/antagonists in such inflammatory diseases is noteworthy. In this study, we aimed to investigate the relationship between hypoxia, adenosine and inflammation, as well as the role of adenosine agonists and antagonists in this situation. Materials and Methods: For this purpose, two different hypoxia models, moderate and severe, were used. Using a total of 80 male Sprague-Dawley rats for both models, 4 subgroups were designed: control (CON), dimethyl sulfoxide (DMSO), adenosine agonist (AGO; CGS-21680) and adenosine antagonist (ANT; MSX-3). Rats were exposed to moderate groups 13% O2 and severe groups 10% O2 in fine-tuned normobaric hypoxia chambers for 7 days. At the end of the 7th day, ventilation measurements were made and the hypoxia model was confirmed. A2AR, CD11c, COX2, NFKB and VEGF antibody expressions were evaluated by immunofluorescence staining method by taking frozen sections from the lung tissues after the experimental stages. Results: This study showed that the expression of inflammation markers increased in experimental hypoxia models. According to the findings, while the levels of A2AR and VEGF were higher in the agonist group compared to the other groups in both models, the levels of inflammatory markers CD11c, NFKB and COX2 were significantly lower. Conclusion: Various natural and synthetic drugs are available as treating the inflammation which can be helpful in treating lung disorders. Researchers are still searching for new anti-inflammatory drugs which can produced faster response. These findings highlight the potential benefit of A2A agonists, which can be used in hypoxia-induced lung inflammation.
Keywords : Hipoksi, adenozin, adenozin agonist/antagonist, akciğer toksisitesi

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