Polyhydroxylated fullerene derivative C₆₀(OH)₂₄ prevents mitochondrial dysfunction and oxidative damage in an MPP⁺-induced cellular model of Parkinson's disease

To find effective agents for Parkinson's disease (PD) prevention and therapy, we examined the protective effects of the polyhydroxylated fullerene derivative C₆₀(OH)₂₄ in a 1-methyl-4-phenylpyridinium (MPP⁺)-induced acute cellular PD model in human neuroblastoma cells and the free radical scavenging effects in this model with an electron spin resonance (ESR) spectrometer. Pretreatment with C₆₀(OH)₂₄ at concentrations greater than 20 μM showed significant protective effects on MPP⁺-induced loss in cell viability, decreases in mitochondrial function (including mitochondrial membrane potential and activities of complex I and II), and increases in the levels of reactive oxygen species and oxidative damage to DNA and proteins. In addition, C₆₀(OH)₂₄ acts as a phase 2 enzyme inducer to protect cells from MPP⁺-induced decreases in expression of nuclear factor-E2-related factor 2, expression and activity of γ-glutamyl cysteine ligase and level of glutathione. The ESR study showed that C₆₀(OH)₂₄ is a powerful radical scavenger for superoxide, hydroxyl, and lipid radicals. These data suggest that C₆₀(OH)₂₄ is a mitochondrial protective antioxidant with direct radical scavenging activity and indirect antioxidant inducing activity.