Nanocapsulated flavonoid: Effect on cerebral ischemia-reperfusion induced mitochondrial oxidative damage in rat brain

Abstract

Mitochondria are the most important source of Reactive Oxygen species. Superoxide anion produced by mitochondria leads to damage to membranes impairing the ability of mitochondria to synthesize ATP and to carry out their wide range of metabolic functions. Thus mitochondria are both the source as well as the target for ROS. Oxidative stress generated in ischemia-reperfusion and other neurodegenerative disorders, distorts the homeostasis between ROS generation in mitochondria and its antioxidant defense for ROS detoxification. The weakened cellular antioxidant level in ageing accelerates mitochondrial oxidative damage also and this contributes to the decrease in efficiency of oxidative phosphorylation associated with ageing. Quercetin (QC), the naturally occurring flavonoid has immense free radical scavenging properties but its clinical application is restricted mostly due to its insoluble nature and inability to circumvent the Blood Brain Barrier like most of the common therapeutics. Nanocapsulated QC (NQC) is an effective approach in combating ischemia- reperfusion induced neurodegeneration. Cerebral ischemia subsequent reperfusion causes a massive damage in rat brain, both for young and aged. NQC treatment exerted a substantial protection against cerebral ischemia reperfusion induced mitochondrial damage. Higher conjugated diene and ROS level in neuronal mitochondria accompanied with a lower GSH were found in aged, compared to sham control young rats. Further loss of those parameters was observed in aged rat brain by cerebral ischemia and reperfusion. NQC treatment resulted a significant protection both in young and old rats, where as, no significant protection was noticed when aged rats were treated with QC. The marked damage in neuronal mitochondrial respiratory enzymes due to ischemia-reperfusion in all age grouped rats was prevented by NQC and protected mitochondria to restore its normal functions.