Comparative study on thiol drugs’ effect on tert-butyl hydroperoxide induced luminol chemiluminescence in human erythrocyte lysate and hemoglobin oxidation

•Three types of chemiluminescence kinetic under influence of thiol drugs.•Various proportion of methemoglobin/hemichromes formation under influence of thiols.•Thiol-derived secondary free radicals can be accelerated by the modification of globin.•Heterogeneity of reaction mechanisms depends on struc...

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Veröffentlicht in:Toxicology in vitro 2015-02, Vol.29 (1), p.148-154
Hauptverfasser: Sajewicz, Waldemar, Zalewska, Marta, Milnerowicz, Halina
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Sprache:eng
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Zusammenfassung:•Three types of chemiluminescence kinetic under influence of thiol drugs.•Various proportion of methemoglobin/hemichromes formation under influence of thiols.•Thiol-derived secondary free radicals can be accelerated by the modification of globin.•Heterogeneity of reaction mechanisms depends on structural relationship of thiol drugs.•Thiol drugs can create danger of propagation and amplification of oxidative stress. The current studies have investigated the effect of heterocyclic drugs with the single thiol group (thiamazole, mercaptopurine) and dithiol aliphatic drugs (dimercaptosuccinic acid, dithiothreitol) under oxidative stress conditions, using tert-butyl hydroperoxide (t-BuOOH), in human erythrocyte lysate with the luminol-enhanced chemiluminescence technique. Knowing that oxidative processes induced by t-BuOOH are triggered by (oxy)hemoglobin (Hb), the effect of different thiol drugs (RSH) on isolated human Hb oxidation to methemoglobin (MHb) and hemichromes (HChr) was further considered. Three types of chemiluminescence curves, fitting to logistic-exponential model, have been revealed under influence of RSH. Structure of the data (MHb and HChr production, and free radical activity of RSH) in Principal Component Analysis visualization and kinetic profiles of chemiluminescence integrate information in terms of the diversity of RSH reaction mechanisms depending on the specific molecular context of the given thiol: aliphatic or aromatic nature as well as the number and position of the –SH groups in the molecule. The study conducted in presented in vitro systems indicates the potential role of thiol drugs mediated toxicity in an oxidative stress dependent mechanism.
ISSN:0887-2333
1879-3177
DOI:10.1016/j.tiv.2014.09.001