Neuroprotective Effects of Mitochondria-Targeted Quercetin Against Rotenone-Induced Oxidative Damage in Cerebellum of Mice

Abstract

Mitochondrial dysfunction leads to various types of metabolic impairments, including decreased ATP formation, diminished calcium buffering, gathering of metabolic intermediates and amplified production reactive oxygen species and reactive nitrogen species. Rotenone is a strong inhibitor of complex I and causes mitochondrial dysfunction, leads to motor impairment, metabolic disorder and cellular damage. Quercetin is a strong antioxidant and neuroprotective against neurodegenerative diseases, but its efficacy is limited because it does not gather into the mitochondria. Therefore, mitochondrially targeted antioxidants have to be developed by conjugating with lipophilic cation which can freely cross through the mitochondrial membrane and protects mitochondrial injury. This study investigated the protective effect of quercetin and mitochondrial-targeted quercetin (MTQ) in rotenone-induced cerebellar toxicity in mice. Treatment of rotenone (3 mg/kg b.w., p.o for 60 days) in mice significantly increases in the levels of lipid peroxidation, nitric oxide and decrease in the activity of AChE, reduced glutathione, superoxide dismutase and catalase were observed in mice compared to controls. Co-treatment of quercetin and MTQ (30mg/kg b.w., p.o) along with rotenone significantly increased AChE activity and protected against rotenone-induced enhanced oxidative stress. Histological study of cerebellum exhibited necrosis of Purkinje cells as revealed by irregular, damaged cells and perineuronal vacuolation in rotenone-treated mice. Co-treatment of quercetin and MTQ along with rotenone showed protection against rotenone-induced cellular damage in these cells. The results exhibit that both quercetin and MTQ showed a protective effect against rotenone-induced cerebellar toxicity in mice and MTQ is more effectively showed protection than quercetin.