IN-VITRO COMPARATIVE-ASSESSMENT OF THE ANTIOXIDANT ACTIVITY OF NACYSTELYN AGAINST 3 REACTIVE OXYGEN SPECIES

Thiol-containing molecules possess antioxidant properties that are of interest in the pharmacological inactivation of reactive oxygen specie s (ROS), particularly in the treatment of chronic inflammatory respira tory 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 (NAG) and captopril. Nacystelyn (GAS 89344 -48-9, NAL) is a L-lysine salt of NAC having demonstrated several adva ntages as compared to NAG. The deoxyribose assay used for assessing th e scavenging effect of drugs against hydroxyl radicals ((OH)-O-.) firs t showed a prooxidant effect for thiols at relatively low concentratio ns that was attributed to a reduction of Fe(III) ions added in the sys tem. This interference could be corrected by increasing ascorbate conc entration. Second order rate constants for reaction with OH were calcu lated by extrapolation of the linear part of competition plots. Both N AL and NAC appeared as potent (OH)-O-. scavengers (Ks > 10(10) mol(-1) s(-1)) and reacted faster than captopril.The horseradish peroxidase a ssay for assessing the activity of thiols against H2O2 could not be us ed because thiol derivatives were substrates for the enzyme. By using the dithio-bis-nitrobenzoic acid (DTNB) assay, first order rate consta nts for reaction with H2O2 were obtained showing that both NAL and NAC reacted quite slowly with this species (K congruent to 0.03 min(-1)) although faster than captopril. Finally, the elastase-alpha(1)-antipro teinase assay for assessing the activity of thiols against HClO again demonstrated the superiority of NAC and NAL over captopril, but this t ime, NAL was more efficient in maintaining the protease/ antiprotease balance than NAG. This last observation may be of importance and deser ves further investigation as HClO has been implicated in lung tissue d amages during inflammatory respiratory diseases.