Influence of Diphenyl Diselenide on Thiol Redox Homeostasis and Electrogenic Membrane Transport in Rotenone-Induced Parkinson’s Disease

Abstract

ABSTRACTThe central role of oxidative stress in the etiology of Parkinsons disease defines a key therapeutic role for antioxidant compounds in the management of the disease. Redox-sensitive proteins such as the Na+/K+-ATPase have also been implicated as one of the targets of oxidative stress. The present study sought to investigate the role of diphenyl diselenide (DPDSe) in amelioration of disturbed redox homeostasis and modulation of enzyme activity caused by rotenone administration to Wistar albino rats. In determining the best route of rotenone administration, animals were grouped into four namely: control, oral, intraperitoneal (IP) and subcutanoeus (SC) and administered rotenone (3mg/kg) via oral, intraperitoneal (IP) and subcutaneous routes, with controls receiving the vehicle (2% DMSO + 98% normal saline (0.85%)). Having observed a more deleterious impact in the with he IP route, this mode of rotenone administration was selected along with oral administration of DPDSe (10mg/kg). this was done with four groups of animals namely: control, DPDSe, rotenone and DPDSe+rotenone. The effect of treatment was evaluated after seven days for total and non-protein thiol levels, lipid peroxidation and Na+/K+-ATPase activity. The result demonstrated the antioxidant potential of DPDSe in attenuating depletion of thiols, and lipid peroxidation caused by rotenone. It is apparent that DPDSe is a promising therapeutic agent in the management of PD, hence further investigations into its impact on different pathways is expedient in the search for an effective treatment for PD.HighlightsIntraperitoneal administration of rotenone gives a comparatively faster development of Parkinson’s disease features in rodentsRotenone mediates depletion of total and non-protein thiol levels in the pathogenesis of Parkinson’s diseaseDiphenyl diselenide significantly attenuates thiol depletion and lipid peroxidation mediated by rotenoneRotenone-mediated inactivation of Na+/K+-ATPase in Parkinson’s disease etiology may involve ATP depletion