Bridgeman M M, Marsden M, Selby C, Morrison D, MacNee W
Department of Biochemistry, University of Edinburgh Medical School.
Thorax. 1994 Jul;49(7):670-5. doi: 10.1136/thx.49.7.670.
Oxidant/antioxidant imbalance may occur in the lungs of patients with chronic obstructive pulmonary disease (COPD). Glutathione is an important extracellular and intracellular thiol oxidant in the lungs. These studies were carried out to determine the effect of N-acetyl cysteine on thiol concentrations in plasma, bronchoalveolar lavage fluid, and lung tissue.
Studies were carried out on normal subjects, patients with COPD, and those undergoing lung resection. In the first study N-acetyl cysteine was given to three groups; healthy subjects (600 mg once daily by mouth) and two groups of patients with COPD. In the first group of patients with COPD the dose was 600 mg once daily and in the second 600 mg thrice daily, all for five days. The latter dosage regimen was also given to six patients before bronchoscopy and to 11 patients before lung resection. Lung glutathione (GSH) levels in bronchoalveolar lavage fluid or lung tissue were compared with the same numbers of patients who did not receive N-acetyl cysteine.
N-acetyl cysteine was detected in plasma after a single 600 mg dose in normal subjects and patients with COPD up to 1.5 hours after the drug was given. Plasma cysteine concentrations increased in normal subjects on both days 1 and 5, and in patients with COPD on day 5. Glutathione concentrations in plasma increased on day 1 in normal subjects but not in patients with COPD given 600 mg N-acetyl cysteine daily. With the higher dose of 600 mg thrice daily, however, there was a sustained elevation of GSH concentrations in plasma in patients with COPD. In patients undergoing routine diagnostic bronchoscopy and bronchoalveolar lavage those who were given N-acetyl cysteine (600 mg) thrice daily for five days had higher concentrations of cysteine in the plasma, but no significant differences in cysteine concentrations in bronchoalveolar lavage or epithelial lining fluid compared with a control group; nor were there any differences in reduced glutathione concentrations in plasma, bronchoalveolar lavage or epithelial lining fluids between the control and treated groups. Moreover, in patients undergoing lung resection those treated with N-acetyl cysteine (600 mg thrice daily for five days) had similar concentrations of cysteine and glutathione in both plasma and lung tissue when compared with a control untreated group.
These data suggest that, even when given in high oral doses, N-acetyl cysteine does not produce a sustained increase in glutathione levels sufficient to increase the antioxidant capacity of the lungs.
慢性阻塞性肺疾病（COPD）患者的肺部可能会出现氧化/抗氧化失衡。谷胱甘肽是肺部一种重要的细胞外和细胞内硫醇氧化剂。开展这些研究以确定N-乙酰半胱氨酸对血浆、支气管肺泡灌洗液和肺组织中硫醇浓度的影响。
对正常受试者、COPD患者和接受肺切除术的患者进行研究。在第一项研究中，将N-乙酰半胱氨酸给予三组；健康受试者（每日口服600毫克，一次）和两组COPD患者。在第一组COPD患者中，剂量为每日600毫克，一次，在第二组中为每日600毫克，三次，均持续五天。在支气管镜检查前对六名患者以及在肺切除术前对11名患者也给予了后一种给药方案。将支气管肺泡灌洗液或肺组织中的肺谷胱甘肽（GSH）水平与未接受N-乙酰半胱氨酸的相同数量患者进行比较。
在正常受试者和COPD患者单次服用600毫克剂量后，直至给药后1.5小时，血浆中检测到N-乙酰半胱氨酸。正常受试者在第1天和第5天血浆半胱氨酸浓度升高，COPD患者在第5天升高。正常受试者在第1天血浆谷胱甘肽浓度升高，但每日给予600毫克N-乙酰半胱氨酸的COPD患者未升高。然而，对于每日三次600毫克的较高剂量，COPD患者血浆中的GSH浓度持续升高。在接受常规诊断性支气管镜检查和支气管肺泡灌洗的患者中，连续五天每日三次给予N-乙酰半胱氨酸（600毫克）的患者血浆中半胱氨酸浓度较高，但与对照组相比，支气管肺泡灌洗或上皮衬液中的半胱氨酸浓度无显著差异；对照组和治疗组之间血浆、支气管肺泡灌洗或上皮衬液中还原型谷胱甘肽浓度也无差异。此外，在接受肺切除术的患者中，与未治疗的对照组相比，接受N-乙酰半胱氨酸治疗（每日三次600毫克，持续五天）的患者血浆和肺组织中的半胱氨酸和谷胱甘肽浓度相似。
这些数据表明，即使大剂量口服，N-乙酰半胱氨酸也不会使谷胱甘肽水平持续升高到足以增强肺部抗氧化能力的程度。
