THIOL OXIDASE AND PEROXIDASE MIMETIC DYNAMICS OF REDOX MODULATORS AS POSSIBLE MODEL IN PREDICTING GLUTATHIONE MODULATION IN VIVO

Abstract

Intriguingly, data emerging from the chemistry, reactivity and pharmacology of organoseleniums with respect to their glutathione peroxidase (GPx) and thiol oxidase (TOx) mimetic properties and glutathione (GSH) modulation in vivo may provide a rational basis for the development of an in vitro model in the prediction of the effect of redox modulators on the GSH biosynthesis in vivo. However, such in vitro model is scanty in the literature. Hence this study utilizes both the chemical [involving the use of exogenous mono- (glutathione and cysteine) and di-thiol (dithiothreitol)] and simple biological [involving the participation of catalytically essential thiols of cerebral sodium pump and hepatic aminolevulinic acid dehydratase] models of GPx and TOx mimetic properties of redox modulators that have hitherto been reported to upregulate (diphenyl diselenide (DPDSe), rutin, quercetin, tannic acid and gallic acid) and downregulate (HgCl2, PbCl2, CdCl2, AlCl3 and KMnO4) GSH level in vivo with a view to predict the relationship between GPx and TOx of these redox modulators and their influence on GSH homeostasis in vivo. Furthermore, the influence of these redox modulators on GSH level and other redox indices was evaluated in vivo. The results showed that with the exception of DPDSe, redox modulators that upregulate GSH in vivo also exhibit GPx mimic but not TOx, whereas, those that downregulate GSH exhibit TOx but not GPx mimic in both chemical and simple biological models. Consequently, there is a strong line of evidence to suggest that any redox modulator that exhibit TOx mimicry may downregulate GSH level, whereas, those with inherent GPx mimicry may upregulate GSH level in vivo. Hence, this study may provide a first line of testing in the rational design and testing of potential medicaments aimed at boosting the level of GSH in vivo, thus circumventing the cumbersome procedures for ethical clearance associated with the use of animal models in drug testing.