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. © 2008 Wiley‐Liss, Inc.