Effect of thiol drugs on tert-butyl hydroperoxide induced luminol chemiluminescence in human erythrocytes, erythrocyte lysate, and erythrocyte membranes.
The paper investigates the effect of thiol drugs (RSH) under oxidative stress condition using luminol-enhanced chemiluminescence technique. The examinations included N-acetylcysteine (NAC), N-acetylpenicillamine (NAP), penicillamine (PEN), mesna (MES), and tiopronin (TPR). The model systems contained isolated human erythrocytes (RBC), erythrocyte lysates (LYS) or erythrocyte membranes (MEM) exposed to tert-butyl hydroperoxide (t-BuOOH). Under the influence of RSH, a bimodal character of some experimental chemiluminescence curves was observed and the kinetic solution was considered as the sum of two logistic-exponential processes. These chemiluminescence changes probably reflected two connected processes--scavenging by RSH of the t-BuOOH-induced free radicals and simultaneous generation of thiol-derived secondary free radicals. Individual differences in thiols interaction showed a multivariate set of the kinetic curve descriptors. The Principal Component Analysis (PCA) well distinguished subsets of RSH influence in systems with RBC or LYS. Generally, the action of NAC was exclusively pro-oxidant in both systems, with RBC and LYS. The behaviour of MES or NAP in these systems was also pro-oxidant but many times less prominent than NAC. Under the influence of TPR a dramatic switch in the anti-oxidant effect was observed in system with RBC to very pro-oxidant effect in LYS. The influence of PEN was analogical to TPR but very weak. This experimental model together with kinetic solution of the unique bimodal chemiluminescence curves, and PCA, supply new insights to the dual (anti- and pro-oxidant) effects of thiol drugs under oxidative stress condition.
Sajewicz
Waldemar
W
Department of Biomedical and Environmental Analyses, Wroclaw Medical University, Grunwaldzka St. 2, PL 50-355 Wroclaw, Poland. sajewicz@tox.am.wroc.pl
D000111:Acetylcysteine / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D049449:Luminescence; D008165:Luminol; D015080:Mesna / Q000494:pharmacology; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D008625:Tiopronin / Q000494:pharmacology; D020122:tert-Butylhydroperoxide / Q000494:pharmacology*
D013438:Sulfhydryl Compounds; C010005:N-acetylpenicillamine; D008165:Luminol; D020122:tert-Butylhydroperoxide; D008625:Tiopronin; D010396:Penicillamine; D015080:Mesna; D000111:Acetylcysteine