title: In vitro comparative assessment of the antioxidant activity of nacystelyn against three reactive oxygen species.
abstract: Thiol-containing molecules possess antioxidant properties that are of interest in the pharmacological inactivation of reactive oxygen species (ROS), particularly in the treatment of chronic inflammatory respiratory diseases. In the present study, the in vitro antioxidant activity of a new agent was examined and compared with other thiol containing molecules, N-acetylcysteine (NAC) and captopril. Nacystelyn (CAS 89344-48-9, NAL) is a L-lysine salt of NAC having demonstrated several advantages as compared to NAC. The deoxyribose assay used for assessing the scavenging effect of drugs against hydoxyl radicals (.OH) first showed a prooxidant effect for thiols at relatively low concentrations that was attributed to a reduction of Fe(III) ions added in the system. This interference could be corrected by increasing ascorbate concentration. Second order rate constants for reaction with OH were calculated by extrapolation of the linear part of competition plots. Both NAL and NAC appeared as potent .OH scavengers (Ks > 10(10) mol-1 s-1) and reacted faster than captopril. The horseradish peroxidase assay for assessing the activity of thiols against H202 could not be used because thiol derivatives were substrates for the enzyme. By using the dithio-bis-nitrobenzoic acid (DTNB) assay, first order rate constants for reaction with H2O2 were obtained showing that both NAL and NAC reacted quite slowly with this species (K approximately equal to 0.03 min-1) although faster than captopril. Finally, the elastase-alpha 1-antiproteinase assay for assessing the activity of thiols against HClO again demonstrated the superiority of NAC and NAL over captopril, but this time, NAL was more efficient in maintaining the protease/antiprotease balance than NAC. This last observation may be of importance and deserves further investigation as HClO has been implicated in lung tissue damages during inflammatory respiratory diseases.
authors.affiliation: Laboratory of Pharmaceutical Chemistry, Free University of Brussels, Belgium.
authors.forename: F
authors.initials: F
authors.lastname: Vanderbist
authors.forename: P
authors.initials: P
authors.lastname: Maes
authors.forename: J
authors.initials: J
authors.lastname: Nève
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000737:chemistry; D000975:Antioxidants / Q000737:chemistry*; D002216:Captopril / Q000737:chemistry; D016166:Free Radical Scavengers / Q000737:chemistry; D006861:Hydrogen Peroxide; D017665:Hydroxyl Radical; D006997:Hypochlorous Acid; D007700:Kinetics; D008239:Lysine / Q000031:analogs & derivatives* / Q000737:chemistry; D017382:Reactive Oxygen Species
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; C086501:N-acetylcysteine lysinate; D017382:Reactive Oxygen Species; D017665:Hydroxyl Radical; D006997:Hypochlorous Acid; D002216:Captopril; D006861:Hydrogen Peroxide; D008239:Lysine; D000111:Acetylcysteine