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

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.

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-α 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.

5-Azacytidine treatment led to restored ∆weight at 14 and 75 days of intervention and NO₂ + 5-Azacytidine significantly reversed the effect of NO₂ exposure on ∆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.

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.