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 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 mu M 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 gamma-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. (c) 2008 Wiley-Liss, Inc.