Sulfhydryl-mediated depression of ciliary activity: an adverse effect of acetylcysteine.

Although N-acetyl-L-cysteine (Mucomyst) is an effective mycolytic, numerous investigations have failed to 
demonstrate a consistent improvement in pulmonary mechanics following its use. In 
order to determine whether its beneficial mucolytic activity might be counterbalanced 
by a deleterious direct effect on cilia, we studied its effect 
on the activity of ciliated epithelium in the ferret tracheal organ 
culture system. N-acetyl-L-cysteine consistently caused progressive time-dependent ciliostasis at concentrations clinically 
employed, with complete ciliary paralysis within 8 hr. The effect was 
only partially reversed by the removal of the drug. Control preparations 
retained full ciliary activity for 3 to 12 weeks. In order 
to determine the active site on the N-acetyl-L- cysteine molecule, we 
investigated the ciliostatic effects of five of its chemical analogs. Isomolar 
N-acetyl-L-alanine was not ciliostatic, indicating the necessity of a sulfhydryl group 
for activity. Ciliostasis was independent of isomeric structure, acetylation, and chain 
length, as evidenced by the similar ciliostatic effects of L-cysteine, D-cysteine, 
2-mercaptoethylamine, and N-acetyl-L-homocysteine. We conclude that N-acetyl-L-cysteine induces partially reversible ciliostasis 
of tracheal epithelium via its sulfhydryl group; prolonged use of this 
drug may impair mucociliary clearance. 