Abstract:
The formation and subsequent reactivity of thiol-mediated selenol derivatives of diorganyl diselenide has been an area of intense study among selenium experts. In this regard, emphasis has been focused on the influence of possible modification of the organic moiety of these organoseleniums on their selenol-derivatives and the attendant therapeutic and toxicological implications. Hence, this study sought to examine the effect of chloro-derivatives of diphenyl diselenide [dichloro- diphenyl diselenide; CDPDS] on its classical glutathione peroxidase (GPx) mimetic therapeutic mechanism. The influence of thiol modifiers [iodoacetamide, IA; and diamide, DA] on the GPx-like catalytic action of CDPDS in various prooxidants provoked cerebral and hepatic lipids peroxidation was investigated at pH range characterizing normal physiology as well pathological acidosis in vitro. Moreso, the possible involvement of essential thiols of the sulphydryl proteins, cerebral sodium pump and hepatic δ-aminolevulinic acid dehydratase (δ-ALAD) in the formation of selenol derivatives of CDPDS was investigated. The results showed that irrespective of the mechanisms of thiol modification employed by IA [an alkylating agent] and DA [a disulphide cross linking agent], these thiol modulators diminished the protective effect of CDPDS against oxidant-induced lipid peroxidation either at physiological or acidic pHs. Additionally, both thiol modifiers inhibited cerebral Na+/K+-ATPase and δ-ALAD and this effect was accompanied by a concomitant diminution in the antioxidant action of CDPDS. Thus, it appears that the classical GPx mimicry-mediated therapeutic potentials of CDPDS via its thiol-mediated formation of its selenol derivative is integrally linked to its toxicity on key sulfhydryl proteins.
