Effect of N-acetyl cysteine on thiol levels.

Effect of N-acetyl cysteine on thiol levels We read with interest the article by Dr Bridge-man and colleagues on the effect of oral N-acetyl cysteine (NAC) on thiol levels in epithelial lining fluid (ELF) and lung tissue (July 1994;49:670-5). Their suggestion that NAC may not be the drug of choice to enhance the glutathione antioxidant potential of the lungs in chronic obstructive pulmonary disease (COPD) is not supported by their data, since levels of cysteine or glutathione in ELF, bronchoalveolar lavage (BAL) fluid, or lung tissue were not measured in these patients. In addition, they did not perform functional measurements. Several studies have investigated the anti-oxidative capacity of NAC, 600 mg daily. In healthy smokers significant decreases in levels of lactoferrin, ECP, and chemotactic activity of neutrophils in BAL fluid, and of myelo-peroxidase and elastase levels in serum, were found.12 Treatment with NAC, 200 mg twice or three times daily for more than one year, was associated with a decrease in the number of bacteria, especially in patients with COPD.3 The design of some of these studies precludes firm conclusions, but they at least suggest that conventional doses of NAC may influence the antioxidative capacity of the lung. This is of special relevance in those patients with a significantly disturbed pulmonary oxidative/antioxidative balance, such as patients with COPD and smokers. Indeed, Lundback et al recently showed that two years of treatment with NAC, 600mg daily, reduced the annual decline in FEV, compared with a control group.4 This effect was most pronounced in smoking patients over 50 years of age with already considerably decreased FEVy. Looking at the pharmacokinetic data, the authors showed in a group of patients consisting of smokers, ex-smokers and non-smokers that NAC, 600 mg daily for five days, increased levels of glutathione in BAL fluid by 180% 1-3 hours after the last dose (p<0 05), and by 24% 16-20 hours after the last dose (NS).5 This "transient" increase in antioxidants in the lung apparently does not preclude a decrease in oxidative stress, or an improvement in antioxidative capacity of the lung, or both. N-acetylcysteine reduces selected humoral markers of inflammatory cell activity in BAL fluid from healthy smokers: correlation to effects on cellular variables.