Idiopathic pulmonary fibrosis (IPF) is characterized by a huge alveolar oxidant burden and a deficiency of glutathione, a major antioxidant, in the pulmonary epithelial lining fluid (ELF). Therefore, a rational therapeutic strategy is to increase lung glutathione to augment the pulmonary antioxidant protective screen.
To evaluate this concept, different doses of N-acetylcysteine (NAC), a glutathione precursor, were administered intravenously to eight patients with pulmonary fibrosis and six control subjects. In patients, bronchoalveolar lavage fluid (BALF) total glutathione increased significantly from 0.99 +/- 0.25 microM to 1.79 +/- 0.37 microM within 3 h following 1.8 g NAC, whereas 4.8 g NAC had no additional effect (1.47 +/- 0.34 microM).
In the control subjects, NAC did not significantly alter BALF total glutathione (baseline: 0.79 +/- 0.17 microM, 600 mg NAC: 0.92 +/- 0.33 microM, 1.8 g NAC: 1.39 +/- 0.41 microM, 4.8 g NAC: 1.33 +/- 0.46 microM). The same was true in ELF, 1.8 g NAC significantly raised ELF total glutathione in patients from 186 +/- 47 microM to near normal levels (373 +/- 103 microM), with no further increase following 4.8 g NAC (293 +/- 62 microM). In the control subjects, ELF total glutathione remained unchanged independent of the NAC dose (baseline: 342 +/- 91 microM, 600 mg NAC: 385 +/- 135 microM, 1.8 g NAC: 633 +/- 220 microM, 4.8 g NAC: 646 +/- 263 microM).
The increases in total glutathione were almost entirely due to increased levels of reduced glutathione, the form functional as an antioxidant. No adverse effects were noted.(ABSTRACT TRUNCATED AT 250 WORDS)
