Non-inflammatory emphysema induced by NO2 chronic exposure and intervention with demethylation 5-Azacytidine

Aims: A rat model of emphysema was established that mimics the features of the human emphysema subtype and explores the effects of demethylation on lung function and blood tests. Materials and methods: Rats were randomly assigned to NO2, NO2+ 5-Azacytidine, and normal air groups based on a emphysema rat model induced by chronic NO2 exposure. This study estimates the characteristics of emphysema by conducting an analysis for IL-6 and TNF-alpha levels in bronchoalveolar lavage fluids (BALF) and plasma. Furthermore, CD68 macrophage immunofluorescent staining and inflammatory cell counts in BALF were compared between rats exposed to NO2 and normal air. Key findings: 5-Azacytidine treatment led to restored Delta weight at 14 and 75 days of intervention and NO2+ 5-Azacytidine significantly reversed the effect of NO2 exposure on Delta weight. Intervention with 5-Azacytidine alleviated the decline of pulmonary function with a significant increase in FEV100/ FVC% at 75 days in NO2+ 5-Azacytidine rats compared to NO2 rats. 5-Azacytidine reduced the counts of white blood cells (WBCs), granulocytes, lymphocytes, and monocytes at 14 days, but increased WBC, granulocyte, and monocyte counts at 45 days. Red blood cell counts, hemoglobin, and hematocrit concentrations were significantly reduced in NO2+ 5-Azacytidine rats. Significance: This non-inflammatory rat emphysema model (induced by chronic NO2 exposure with global DNA hypomethylation and demethylation therapy with 5-Azacytidine) effectively improved emphysema by alleviating the decline of lung function and hypoxia, and slightly reinforced immune function. These results indicate the therapeutic potential of demethylation agents for the prevention and treatment of emphysema induced by the air pollutant NO2.