Methods and Findings in Experimental and Clinical Pharmacology
Vol. 24, Suppl. A, 2002, pp. 39
ISSN 0379-0355
Copyright 2002 Prous Science, S.A.
CCC: 0379-0355/2002
http://www.prous.com

N-acetylcysteine Review: Back to the Future

M. Farré and ¹J. Morera

IMIM, Departamento de Farmacología Clínica, Barcelona; ¹Hospital Germans Trias i Pujol, Badalona, Spain

N-acetylcysteine (NAC) has been widely used as a mucolytic for the treatment of chronic obstructive pulmonary disease (COPD). NAC has a sulphydryl group that can reduce disulfide bonds and decrease mucus viscosity. NAC may act as an antioxidant drug because it serves as a precursor for intracellular synthesis of glutathione (GSH) (1). For years NAC has been used as an antidote in the treatment of acetaminophen (paracetamol) poisoning because of its capacity to enhance GSH production.

In recent years, new basic research and clinical results have renewed interest in NAC as an antioxidant therapy. In animal models, NAC has been shown to reduce the oxidative stress associated with reactive oxygen species and the cytokines produced by immune cells (2). NAC decreased hydrogen peroxide-induced damage in epithelial cells (3), suppressed heat-provoked lipid peroxidation in lung homogenates and decreased endotoxin-induced accumulation of inflammatory markers in lungs (4). In humans, oral NAC reduced the levels of selected inflammatory markers in bronchoalveolar lavage fluid of asymptomatic cigarette smokers and decreased lipid peroxidation in patients with COPD (1). The clinical efficacy of NAC has been investigated in COPD. Because of its antioxidant activity, long-term treatment with NAC reduces the risk of acute exacerbation and days of illness, thereby decreasing morbidity and health costs associated with disease (5-7). These findings support the data observed in the prevention of symptomatic viral disease and bacterial colonization. Recently, the Global Obstructive Lung Disease (GOLD) guidelines have recommended the use of NAC in preventing acute exacerbations in COPD patients (8).

The antioxidative actions of NAC are now under investigation for other diseases that involve antioxidative stress and inflammatory markers, such as idiopathic pulmonary fibrosis, cardiovascular disease and Parkinson's disease. Very recent clinical trials in renal protection (9, 10) have demonstrated a future role for NAC in the prevention of extrapulmonary diseases.

REFERENCES

1. Repine, J.E., Bast, A., Lankhorst, I. Oxidative stress in chronic obstructive pulmonary disease. Oxidative Stress Study Group. Am J Respir Crit Care Med 1997, 156: 341-57.

2. Linden, M., Rasmussen, J.B., Piitulainen, E. et al. Airway inflammation in smokers with nonobstructive and obstructive chronic bronchitis. Am Rev Respir Dis 1993, 148: 1226-32.

3. Dekhuijzen, P.N.R., Aben, K.K., Dekker, I. et al. Increased exhalation of hydrogen peroxide in patients with stable and unstable chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1996, 154: 813-6.

4. Rubio, M.L., Sanchez-Cifuentes, M.V., Ortega, M. et al. N-acetylcysteine prevents cigarette smoke induced small airways alterations in rats. Eur Respir J 2000,15: 257-64.

5. Stey, C., Steurer, J., Bachmann, S., Medici, T.C., Tramer, M.R. The effect of oral N-acetylcysteine in chronic bronchitis: A quantitative systemic review. Eur Respir J 2000, 16: 253-62.

6. Granjean, E.M., Berthet, P., Ruffmann, R., Leuenberger, P. Efficacy of oral long-term N-acetylcysteine in chronic bronchopulmonary disease: A meta analysis of published double-blind, placebo-controlled clinical trials. Clin Ther 2000, 22: 209-21.

7. Granjean, E.M., Berthet, P., Ruffmann, R., Leuenberger, P. Cost-effectiveness analysis of oral N-acetylcysteine as a preventative treatment in chronic bronchitis. Pharmacol Res 2000, 42: 39-50.

8. GOLD (www.goldcopd.com).

9. Tepel, N., van der Giet, M., Schwarzfeld, C., Lanfer, M., Liermann, D., Zidek, W. Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med 2000, 343: 180-4.

10. Diaz-Sandoval, L.J., Kosowsky, B.D., Losordo, D.W. Acetylcysteine to prevent angiography-related renal tissue injury (the APART trial). Am J Cardiol 2002, 89: 356-8.

Methods and Findings in Experimental and Clinical Pharmacology Vol. 24, Suppl. A, 2002, pp. 39
ISSN 0379-0355 Copyright 2002 Prous Science, S.A. CCC: 0379-0355/2002 http://www.prous.com