N-acetyl-l-cysteine (NAC), a derivative of the naturally occurring
amino acid l-cysteine, is a
mucolytic agent that may also act as an
antioxidant by providing
cysteine intracellularly for increased production of
glutathione. It is also used for the treatment of
acetaminophen overdose. Areas covered: The recent international recommendations for the treatment of
chronic obstructive pulmonary disease (
COPD) report that NAC, because of its
mucolytic activity, reduces acute exacerbation of
COPD (AECOPD) with a modest improvement in health status. However, NAC is a pleiotropic
drug with heterogeneous pharmacologic characteristics that certainly include
mucolytic activity, but also has anti-infective properties and specific
antioxidant and anti-inflammatory effects in the airways. Thus, the mechanisms leading to the protective role of this agent against AECOPD need to be adequately addressed. Expert commentary: The protective effect of NAC against AECOPD seems to be related not only to its well-documented
mucolytic activity but also to activation of
antioxidant pathways, inhibition of
pro-oxidant and inflammatory pathways, and modulation of human bronchial tone. Thus, the dogma that NAC acts prevalently as a
mucolytic agent is outdated, and the hypothesis that its anti-inflammatory effect is secondary to the
antioxidant activity has been rejected.