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

Abstract To find effective agents for Parkinson's disease (PD) prevention and therapy, we examined the protective effects of the polyhydroxylated fullerene derivative C 60 (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 C 60 (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, C 60 (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 C 60 (OH) 24 is a powerful radical scavenger for superoxide, hydroxyl, and lipid radicals. These data suggest that C 60 (OH) 24 is a mitochondrial protective antioxidant with direct radical scavenging activity and indirect antioxidant inducing activity. © 2008 Wiley‐Liss, Inc.