Effects of a new compound (Zy 15850A) on cigarette smoke-induced bronchitis in the rat.

The effect of 4H-4 phenylthieno-(3,2-C)-(1)-benzopyran-2-carboxylate (Zy 15850A) on mucous cell hyperplasia was examined in vivo using a well established rat model of cigarette smoke-induced bronchitis. Zy 15850A was given by gavage (25 mg/kg body weight) to male rats before and after sub-acute exposure (i.e. daily for 14 days) to an atmosphere of cigarette smoke (CS). CS significantly increased the thickness of the epithelium at three of the four sites studied in the trachea and in both of the intrapulmonary levels examined. CS increased the number of epithelial mucous cells in all intrapulmonary airways and also increased the mass of submucosal gland present in the larynx and upper trachea. Zy 15850A completely inhibited CS-induced increases in epithelial thickness in the upper trachea and the two intrapulmonary airway levels studied, and tended to inhibit CS-induced epithelial mucous cell hyperplasia in all the six intrapulmonary airway levels examined, with statistically significant inhibition in two. Zy 15850A had no inhibitory effect of the CS-induced enlargement of laryngo-tracheal submucosal glands. We conclude that, in the rat, the predominant inhibitory effect of Zy 15850A is on CS-induced epithelial thickening with weaker inhibitory effects on mucous cell hyperplasia and enlargement of submucosal glands. Zy 15850A is less effective than other mucoregulatory drugs or antiinflammatory agents we have tested in the same bronchitic model.