Antioxidant and Anti-inflammatory Efficacy of NAC in the Treatment of COPD: Discordant in Vitro and in Vivo Dose-effects: a Review

In order to develop efficient therapeutic regimes for chronic obstructive pulmonary disease (COPD), N-acetylcysteine (NAC) has been tested as a medication which can suppress various pathogenic processes in this disease. Besides its well-known and efficient mucolytic action, NAC meets these needs by virtue of its antioxidant and anti-inflammatory modes of action. NAC is a thiol compound which by providing sulfhydryl groups, can act both as a precursor of reduced glutathione and as a direct ROS scavenger, hence regulating the redox status in the cells. In this way it can interfere with several signaling pathways that play a role in regulating apoptosis, angiogenesis, cell growth and arrest and inflammatory response. Overall, the antioxidant effects of NAC are well documented in in vivo and in vitro studies. It successfully inhibits oxidative stress at both high and low concentrations, under acute (in vitro) and chronic administration (in vivo). With regard to its anti-inflammatory action, in contrast, the effects of NAC differ in vivo and in vitro and are highly dose-dependent. In the in vitro settings anti-inflammatory effects are seen at high but not at low concentrations. On the other hand, some long-term effectiveness is reported in several in vivo studies even at low dosages. Increasing the dose seems to improve NAC bioavailability and may also consolidate some of its effects. In this way, the effects that are observed in the clinical and in vivo studies do not always reflect the success of the in vitro experiments. Furthermore, the results obtained with healthy volunteers do not always provide incontrovertible proof of its usefulness in COPD especially when number of exacerbations and changes in lung function are chosen as the primary outcomes. Despite these considerations and in view of the present lack of effective therapies to inhibit disease progression in COPD, NAC and its derivatives, because of their multiple molecular modes of action, remain promising medication once doses and route of administration are optimized.