INFLUENCE OF DIPHENYL DISELENIDE ON NICKEL AND CHROMIUM MEDIATED HYDROXYL AND THIYL RADICAL ASSAULTS OF BIOMOLECULES.

Abstract

Emerging data have consistently shown that metal toxicity in mammalian system is linked to oxidative stress and the use of antioxidant are considered as intervention strategy. However, the precise biochemical events associated with metal-induced stress and mechanism of action of antioxidants are yet to be fully clarified and thus still open. Thus, this study aimed at investigating the influence of diphenyl diselenide [DPDSe] on nickel sulphate [Ni2+], potassium chromate [Cr3+] and potassium dichromate [Cr6+] mediated hydroxyl and thiyl radical assaults of deoxyribose sugar, cerebral, hepatic and renal lipids. Furthermore, the effect of Ni2+, Cr3+ and Cr6+ on oxidation of dithiothreitol and the activities of hepatic and renal delta aminolevulinic acid dehydratase (δ-ALA-D) were also determined. Finally, 0.25 mg/kg bw each of Ni2+, Cr3+ and Cr6+ were orally administered into rats and treated with 10 mg/kg bw of DPDSe for 30 days. Thereafter the antioxidant status of the cerebral, hepatic and renal tissues were evaluated. Also the activities of redox sensitive enzymes, purine-dependent signaling enzymes and some toxicological enzymes markers were determined. The results showed that Ni2+-induce degradation of deoxyribose via the formation of thiyl radicals while Cr3+ and Cr6+ mediated deoxyribose degradation via hydroxyl radical formation. Moreso, the metals oxidized dithiothreitol and inhibit the activity of the hepatic and renal ð-ALAD. Interestingly, DPDSe diminished the pro-oxidative effects of Ni2+ on deoxyribose degradation and lipid peroxidation in the presence of thiols. Finally, DPDSe also ameliorated redox stress, prevented the inhibition of thiol-containing enzymes and restored the elevated level of the activities of purinergic enzymes and serum enzymes biomarkers that were induced by the metals in vivo. Consequently, the present data suggest that DPDSe is a potent antioxidant candidate in the management of Ni2+, Cr3+ and Cr6+ mediated oxidative stress.