Original Articles
Manorama Singh and PW Ramteke
Abstract
Reduced glutathione (GSH) is an important and abundant non-enzymatic antioxidant in the mitochondria. GSH pool in the mitochondria is maintained by the GSH transport from cytosol and recycling of oxidized glutathione (GSSG) to GSH by NADPH dependent enzymes. GSH quench the reactive oxygen species (ROS) produced in mitochondria. CP, a widely used anti-cancer drug, high dose of it induces hepatotoxicity. CP induced hepatotoxicity is mainly due to depletion of GSH in the mitochondria and thereby oxidative damage. Fisetin, a dietary flavonol, found in fruits and vegetables, has been reported to protect kidney and liver against ROS by modulating the antioxidant enzymes of cytosol. In addition it has been reported that fisetin also up regulated the level of GSH in vitro. No report available on modulation of GSH level by fisetin in mitochondria in vivo. Therefore, we hypothesized that modulation of mitochondrial GSH (mGSH) level by fisetin could be a protective mechanism against the CP induced oxidative damage in mitochondria. Single dose of fisetin (100mg/Kg body wt.) was evaluated against single dose of CP (6 mg/ Kg body wt.) in vivo in mice taking appropriate controls. After experiment biochemical parameters were evaluated in the isolated liver mitochondria. Cisplatin induced depletion of GSH thereby upregulated the ROS level. Consequence of it ROS mediated lipid peroxidation (MDA level) and caspase 3 activation in cytosol. Fisetin restored the GSH level up to normal and thereby decreased level of ROS and ROS mediated consequences.