Background: Human obstructive airway diseases are histopathologically characterized by inflammatory cell infiltration, goblet cell hyperplasia, and mucus hypersecretion in airways. We prepared a rat model of airway injury by exposure of sulfur dioxide (SO2) and then evaluated the effects of S-carboxymethylcysteine (S-CMC), a mucoregulant. Methods: Rats were exposed to SO2 gas for 44 days and orally given S-CMC at 250 mg/kg, twice daily, from 21 to 44 days of exposure for histopathological and immunohistochemical evaluation. Results: SO2 exposure induced inflammatory cell infiltration and mucus cell increase in rat airways. S-CMC treatment significantly decreased this inflammatory cell infiltration in proximal and peripheral airways. Morphometrically, SO2 exposure significantly increased the number of Alcian blue (pH 2.5)- and periodic acid-Schiff (AB/PAS)-positive cells in rat airways (11.8 × 10–2 cell/nuclear profiles per micrometer basement membrane) compared to normal rat airways (1.6 × 10–2 cell/nuclear profiles per micrometer basement membrane). S-CMC treatment significantly decreased the number of AB/PAS-positive cells (4.4 × 10–2 cell/nuclear profiles per micrometer basement membrane, p < 0.01 vs. SO2-exposed rats). Immunohistochemically, SO2 exposure increased the expression of mucin 5AC (MUC5AC) protein in the airway epithelium of rats, but S-CMC treatment inhibited the increase. Conclusions: The increased mucus cells and MUC5AC protein expression seem associated with SO2-induced airway inflammation in rats. The fact that S-CMC suppresses airway inflammation and the increase in mucus cells and MUC5AC protein expression suggests that this mucoregulant may be advantageous in the treatment of inflammatory airway diseases with goblet cell hyperplasia.

Keywords:
Airway Inflammation, Goblet cell hyperplasia, S-carboxymethylcysteine, Alcian blue (pH 2.5)/periodic acid-Schiff, Mucin 5AC immunohistochemistry
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2004
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