DYNAMICS BETWEEN THE TOXICOLOGY AND PHARMACOLOGY OF DIMETHOXYL DIPHENYL DISELENIDE: THE ROLE OF PROTEIN AND NON-PROTEIN THIOLS

Abstract

The antioxidant action of organoselenium has been integrally linked with their glutathione peroxidase (GPx) mimetic activity which is related to thiol consumption. Consequently, the relationship between the oxidation of protein and non-protein thiols by organoselenium compounds and their utilization in their antioxidant action or pharmacologic activity is yet to be fully elucidated. The present study was designed to investigate the influence of protein and non-protein thiols on the toxicology and pharmacology of dimethoxyl diphenyl diselenide (MDPDS) under in vitro experimental model. The influence of dithiothreitol (DTT) on the antioxidant action of MDPDS against oxidant-induced deoxyribose degradation was investigated. Furthermore, iodoacetamide, a thiol oxidant, was employed in this study to investigate the influence of protein thiols on the anti-lipid peroxidation action of MDPDS. Lastly, the effect of iodoacetamide and MDPDS on the activities of sulphydryl enzymes such as delta aminolevulinic acid dehydratase (δ-ALAD) and sodium pump was investigated. Results showed that MDPDS markedly prevented deoxyribose degradation in the presence of DTT but not in the absence of DTT. Furthermore, under in vitro conditions, iodoacetamide markedly reduced the ability of MDPDS to inhibit production of thiobarbituric acid reactive substances (TBARS). Also, while iodoacetamide and MDPDS markedly inhibited the activity of δ-ALAD, only MDPDS inhibited the activity of sodium pump in a concentration-dependent manner. Apparently, considering the similar effect exerted by both iodoacetamide and MDPDS on the activity of δ-ALAD, it is reasonable to speculate that the sulphydryl group on this enzyme is a possible source of thiol utilised by MDPDS to effect its GPx mimetic antioxidant action against the formation of TBARS in tissue homogenates.