Assessment of the antioxidant activity of the SH metabolite I of erdosteine on human neutrophil oxidative bursts.
Acute and chronic lung diseases both lead to an extensive recruitment of neutrophils in the lungs. These cells play a major defensive role but, when activated, they are also an important source of reactive oxygen species, which generate a cytotoxic oxidant stress that triggers a self-sustaining phlogogenic loop. Erdosteine (CAS 84611-23-4) is a mucoactive drug whose metabolization leads to active metabolites with an SH group, and molecules bearing an SH group are also considered to have antioxidant activity. Luminol amplified chemiluminescence was used to investigate the oxidative bursts of human neutrophils and it was found that concentrations of 2.5, 5, 10 and 20 micrograms/ml of metabolite I of erdosteine significantly inhibit oxidative bursts in a concentration-related manner that overlaps the inhibition induced by the control drug N-acetylcysteine. Chemiluminescence was also studied in cell-free systems to see whether the drug also has direct scavenger activity, which was observed from 2.5 to 20 micrograms/ml of metabolite I using the xanthine/xanthine oxidase assay and at concentrations of 0.039 to > or = 2.5 micrograms/ml using the highly-sensitive hypochlorous acid/H2O2 assay. The findings indicate that the metabolite I of erdosteine has antioxidant activity which, together with the drug's mucomodifying activity, may lead to a useful antiphlogistic effect.
Braga
P C
PC
Center for Respiratory Pharmacology, School of Medicine, University of Milan, Italy. bragapc@mailserver.unimi.it
Dal Sasso
M
M
Zuccotti
T
T
D000117:Acetylglucosamine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D002474:Cell-Free System; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008163:Luminescent Measurements; D008165:Luminol; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D016897:Respiratory Burst / Q000187:drug effects*; D013864:Thioglycolates / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*; D014969:Xanthine Oxidase / Q000378:metabolism
D000975:Antioxidants; D016166:Free Radical Scavengers; D013864:Thioglycolates; D013876:Thiophenes; D008165:Luminol; C048498:erdosteine; D006861:Hydrogen Peroxide; D014969:Xanthine Oxidase; D000117:Acetylglucosamine