Abstract:
Progressions in free radicals mediated degenerative diseases are often characterized by diverse and excessive generation of reactive oxygen species and oxidant systems and thus management of such diseases may require combined antioxidants interventions. Since drug-drug interactions can generate additive, synergistic or antagonistic effect, the testing of combination of antioxidants with a view to exploit their improved efficacy in the management of such degenerative diseases becomes highly imperative. The present study sought to investigate the influence of reduced glutathione (GSH) and vitamin C (vit C) on the antioxidant potency of quercetin under in vitro and in vivo conditions. The in vitro antioxidant potency was tested by evaluating the influence of vitamin C and GSH on 2, 2-diphenyl-1-picrylhydrazyl (DPPH), 2, 2’-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and hydroxyl radicals scavenging property of quercetin. In addition, the influence of GSH and vitamin C on the effectiveness of quercetin to inhibit cerebral lipid peroxidation mediated by various potent neurotoxins (Fe2+, H2O2, sodium oxalate, 3-nitropropionic (3-NP) and quinolinic acids (QA)) exhibiting diverse prooxidative mechanisms was also investigated. Furthermore, the influence of both GSH and vit C on the in vivo antioxidant potency of quercetin was tested in rat model of Huntington disease (HD). The results show that under in vitro situation, GSH generally enhanced the radical scavenging properties as well as the ability of quercetin to inhibit cerebral lipid peroxidation initiated either via Fenton reaction or over-activation of glutamate N-methyl-D-aspartate (NMDA) receptors or disturbed mitochondrial function whereas vit C does not. In addition, under in vivo condition, GSH also enhanced the ability quercetin to attenuate the attendant increase in oxidative stress indices and increased activity of purinergic-dependent signaling enzymes (5’-nucleotidase and NTPDase) associated with HD pathophysiology in rats. Furthermore, GSH also boosted the ability of quercetin to restore the low activity of cerebral sodium-potassium ATPase that biochemically characterize HD. In conclusion, combination of quercetin with GSH may further be exploited as therapeutic intervention in the management of progression of oxidative stress situations in degenerative diseases.
