Oxidative stress and
mitochondrial dysfunction are two pathophysiological factors often associated with the neurodegenerative process involved in
Parkinson's disease (PD). Although,
6-hydroxydopamine (6-OHDA) is able to cause dopaminergic neurodegeneration in experimental models of PD by an oxidative stress-mediated process, the underlying molecular mechanism remains unclear. It has been established that some
antioxidant enzymes such as
catalase (CAT) and
superoxide dismutase (SOD) are often altered in PD, which suggests a potential role of these
enzymes in the onset and/or development of this multifactorial syndrome. In this study we have used high-resolution respirometry to evaluate the effect of
6-OHDA on mitochondrial respiration of isolated rat brain mitochondria and the
lactate dehydrogenase cytotoxicity assay to assess the percentage of cell death induced by
6-OHDA in human
neuroblastoma cell line SH-SY5Y. Our results show that
6-OHDA affects mitochondrial respiration by causing a reduction in both respiratory control ratio (IC(50) = 200 ± 15 nM) and state 3 respiration (IC(50) = 192 ± 17 nM), with no significant effects on state 4(o). An inhibition in the activity of both complex I and V was also observed.
6-OHDA also caused cellular death in human
neuroblastoma SH-SY5Y cells (IC(50) = 100 ± 9 μM). Both SOD and CAT have been shown to protect against the toxic effects caused by
6-OHDA on mitochondrial respiration. However, whereas SOD protects against 6-OHDA-induced cellular death, CAT enhances its cytotoxicity. The here reported data suggest that both
superoxide anion and hydroperoxyl radical could account for
6-OHDA toxicity. Furthermore, factors reducing the rate of
6-OHDA autoxidation to its p-
quinone appear to enhance its cytotoxicity.