Idebenone is a
coenzyme Q10 analog and an
antioxidant that has been used clinically to treat
Friedreich Ataxia. Being an
antioxidant,
idebenone could have potential therapeutic potential to treat other
neurodegenerative diseases such as
Parkinson's disease in which oxidative stress plays a role in their pathogenesis. But whether
idebenone can be used to treat
Parkinson's disease has not been evaluated. In this study, we found that exposure of the dopaminergic
neuroblastoma SHSY-5Y cells to 1-10 μM
idebenone for 72 h had no effect on the cell viability revealed by
trypan blue exclusion assay and MTT assay. However, cells exposed to 25 μM or higher concentrations of
idebenone showed extensive
trypan blue-positive staining and significant reduction in cell viability revealed by MTT assay indicating that most of the cells were no longer viable.
Idebenone-induced cell death was characterized by genomic DNA fragmentation and accumulation of
cytochrome c in the cytosol indicating that the death was apoptotic in nature. In addition,
idebenone induced an increase in the total
RNA of the pro-apoptosis
protein BAX, it also increased the
caspase-3 activity in the cell lysates when compared with the untreated control cells or cells exposed to 10 μM or lower concentrations of
idebenone. The detrimental effect of
idebenone was attenuated by
glutathione, an
antioxidant, suggesting that oxidative stress contributed to the
idebenone-induced cell death. In conclusion, our results suggest that
antioxidant idebenone induced apoptosis when used in high concentrations.