Cotgreave I A, Eklund A, Larsson K, Moldéus P W
Eur J Respir Dis. 1987 Feb;70(2):73-7.
Six healthy volunteers underwent bronchoalveolar lavage (BAL) before and after receiving N-acetylcysteine (NAC) 600 mg daily for 2 weeks. Free and total NAC, cysteine and glutathione were determined in the lavage fluid, lavage cells and plasma. No NAC was demonstrated, free or bound in disulfides, in either of the lavage components; furthermore, the cysteine and glutathione content of these components and their respective redox states were unaltered during therapy. Plasma free and total cysteine content was unaltered by administration of the drug, but both free and total plasma glutathione increased significantly. Free NAC could not be detected in plasma following dosing. However, a mean of 0.3 nmol/100 microliters plasma was released from disulfides in plasma following reduction with dithiothreitol. N-acetylcysteine has been proposed to act as a mucolytic by cleavage of disulfide bonds. Our findings do not support this direct mode of action and alternative mechanisms of action must be sought.
六名健康志愿者在每日服用600毫克N-乙酰半胱氨酸（NAC）两周前后接受了支气管肺泡灌洗（BAL）。对灌洗液、灌洗细胞和血浆中的游离和总NAC、半胱氨酸和谷胱甘肽进行了测定。在任何一种灌洗成分中均未检测到游离或结合在二硫键中的NAC；此外，这些成分中的半胱氨酸和谷胱甘肽含量及其各自的氧化还原状态在治疗期间未发生改变。给药后血浆游离和总半胱氨酸含量未改变，但血浆游离和总谷胱甘肽均显著增加。给药后血浆中未检测到游离NAC。然而，用二硫苏糖醇还原后，血浆中二硫键平均释放出0.3纳摩尔/100微升血浆。有人提出N-乙酰半胱氨酸通过裂解二硫键发挥黏液溶解作用。我们的研究结果不支持这种直接作用方式，必须寻找其他作用机制。
