INFLUENCE OF BLOCKAGE OF FREE AND BOUND CEREBRAL HYDROPHILIC THIOLS ON THE GLUTATHIONE PEROXIDASEMIMICRY OF DIPHENYL DISELENIDE

Abstract

The central antioxidant chemistry of diphenyl diselenide (DPDS) has been largely related to its glutathione peroxidase (GPx) mimicry and this implies that a thiol source is critical to its antioxidant activity. However, the possible source of thiols for the glutathione peroxidase mimicry of diphenyl diselenide remains a puzzle. The present study sought to determine the effect of blockage of protein thiols in brain and spinal homogenates on the glutathione peroxidase mimicry of diphenyl diselenide under in vitro experimental model. The antioxidant potency of DPDS against various prooxidants –induced cerebral and spinal lipid assaults was tested in the presence and absence of iodoacetamide (IAC). Furthermore, the possible involvement of thiols of cerebral Na+/K+-ATPase and δ – aminolevulinate dehydratase (δ-ALAD) was also investigated. The results showed that the antioxidants potency of diphenyl diselenide was significantly reduced in the presence of the thiol oxidizing agent-iodoacetamide. This effect correlated with the inhibition of δ-ALAD by IAC and DPDS suggesting that both IAC and DPDS may be competing with thiol on the enzyme. Conversely, while DPDS inhibited Na+/K+-ATPase, IAC did not. Since, IAC can oxidize hydrophilic thiols, it is possible to speculate that the highly lipophilic DPDS may be oxidizing the hydrophobic thiols of Na+/K+-ATPase to effect its antioxidant (GPx) mimicry. Summarily, DPDS may be utilizing thiols on sulphydryl proteins to effect its antioxidant property suggesting a strong dynamics between its toxicology and pharmacology.