[N-acetylcysteine: a functional oxygen radical scavenger in vitro and ex vivo in monocytes and neutrophilic granulocytes of patients with COPD].
In order to develop an efficient antioxidant therapeutic regime for inflammatory disease in the lung N-acetylcysteine (NAC) and reduced glutathione (GSH) were tested to inhibit O2 and H2O2 in vitro and ex vivo. NAC and GSH inhibited both at > or equal to 10(-4)M significantly H2O2 (5 x 10(-8)) mol/ml; p < 0.05). In contrast, in an assay consisting of xanthine/xanthine oxidase/ferricytochrome c Cu++/Zn++ superoxide dismutase (SOD), but not NAC and GSH had an anti-O2 effect (SOD: at > or equal to 10(-5)M, p < 0.01 when compared with 0). In accordance with these results, NAC and GSH had good anti-H2O2 efficacy in freshly isolated and ex vivo cultured mononuclear (MN) and polymorphonuclear cells (PMN) derived from patients with COPD (smoker, n = 30). Both drugs reduced H2O2 significantly when used in concentrations already at > or equal to 10(-9)M (p < 0.05). However, neither GSH nor NAC influenced O2 produced by these inflammatory cells effectively. Antioxidative properties of NAC are well explained by the SH-group within the molecular structure which can be oxidized by certain oxygen radicals. Good H2O2 scavenger function ex vivo, which seems to contradict the results obtained in vitro, illustrates additional cellular GSH-precursor efficacy of both substances in cell dependent assay systems. Thus, to achieve direct anti-H2O2 efficacy in vivo high local NAC concentrations (10(-4)M)) are necessary.
Jaworska
M
M
Berufsgenossenschaftliche Kliniken Bergmannsheil-Universitätsklinik, Abt. für Pneumologie und Allergologie, Bochum.
Gillissen
A
A
Schärling
B
B
Wickenburg
D
D
Schultze-Werninghaus
G
G
D000111:Acetylcysteine / Q000627:therapeutic use*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D005609:Free Radicals; D005978:Glutathione / Q000627:therapeutic use; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000188:drug therapy* / Q000276:immunology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D017382:Reactive Oxygen Species / Q000378:metabolism*
D016166:Free Radical Scavengers; D005609:Free Radicals; D017382:Reactive Oxygen Species; D005978:Glutathione; D000111:Acetylcysteine