INFLUENCE OF ENZYMIC THIOLS ON GLUTATHIONE PEROXIDASE MIMICRY OF DIPHENYL DISELENIDE IN OXIDATIVE STRESS MEDIATED TYPE II DIABETES

Abstract

Several reports have shown that diphenyl diselenide [DPDSe] is a promising medicament in the management of oxidative stress-linked degenerative diseases including diabetes. The chemistry and resulting pharmacological action of DPDSe has been linked to the oxidation of varieties of thiols of biological relevance. However, there is a dearth of information describing the influence of thiols on the pharmacological action of DPDSe in situation of long and persistent diabetes. Herein, the effect of thiol modifiers [diamide (DA) and iodoacetamide (IA)] on glutathione peroxidase mimicry (GPx)-linked antioxidant action of DPDSe in brain and liver tissue homogenate was investigated. In addition, the influence of catalytically relevant thiols of membrane bound ouabain-sensitive electrogenic sodium pump and delta-aminolevulinic acid dehydratase on the antioxidant action of DPDSe was also carried out. Finally, the pharmacological potential of DPDSe in various models of streptozotocin-induced diabetes was also carried out. The results obtained shows that the antioxidant potency of DPDSe was reduced in the presence of the thiol modifiers (DA and IA). Moreso, the thiol modifiers exerted marked inhibitory effect on the activities of both sodium pump and delta-ALAD with concomitant decrease in the antioxidant potency of DPDSe. More interestingly, DPDSe considerably reduced elevated glucose level in all diabetic models left untreated for 3, 14, 30 and 60 days prior to DPDSe administration. In addition, DPDSe profoundly restored redox imbalance and associated dysfunctions in the activities of redox-sensitive enzymes associated with diabetes. Furthermore, DPDSe ameliorated toxicological markers, disturbed lipid profile and hematological indices associated with diabetes. Finally, inhibition of sulfhydryl enzyme [sodium pump] in diabetic condition was restored in the presence of dithiothreitol. Consequently, it appears that the antioxidant chemistry of DPDSe is integrally related to its thiol-linked GPx mimetic property either in vitro or in situations of different models of prolonged and untreated diabetic animals.