Antioxidative and clinical effects of high-dose N-acetylcysteine in fibrosing alveolitis. Adjunctive therapy to maintenance immunosuppression.

作者: CLAUS VOGELMEIER , JÜRGEN BEHR , KONRAD MAIER , BARBARA DEGENKOLB , FRITZ KROMBACH

DOI: 10.1164/AJRCCM.156.6.9706065

关键词: Pulmonary fibrosisLungGlutathioneBronchoalveolar lavageGlutathione disulfideAntioxidantPharmacologyImmunologyAcetylcysteineOxidative stressMedicine

摘要: In fibrosing alveolitis (FA), activated phagocytes cause excessive oxidative stress in the lower respiratory tract. Additionally, levels of glutathione, a major antioxidant human lung, are markedly reduced. Since N-acetylcysteine (NAC) is known precursor for glutathione synthesis, we investigated effect NAC on redox balance and lung function FA. Eighteen patients with an established diagnosis FA were treated 600 mg three times daily 12 wk addition to their latest immunosuppressive therapy. Before after therapy, pulmonary tests (PFTs) bronchoalveolar lavage (BAL) performed. BAL fluid was analyzed regard cell differential, status, methionine sulfoxide content proteins (Met(O)), as indicator at alveolar surface. There increase total (GSHt = GSH +/- 2 x GSSG: 3.43 0.30 microM versus 4.20 0.66 microM, p < 0.05) reduced (GSH: 2.58 0.24 3.42 0.54 0.005) native epithelial lining (GSHt: 267.3 26.0 367.1 36.0 0.005; GSH: 204.5 20.7 302.9 32.2 0.005). The accompanied by decrease Met(O) (6.83 0.71% 4.60 0.40%, PFTs significantly improved during treatment. We conclude that high-dose screen lungs elevating levels. Moreover, indicated These biochemical changes improvement under maintenance immunosuppression. supplementation should, therefore, be considered adjunct therapy

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