Biological markers of oxidative stress in mitochondrial myopathies with progressive external ophthalmoplegia.

According to experimental models suggesting that overproduction of oxygen free-radicals may occur when the electron transport in the respiratory chain is impaired, we searched for in vivo biological markers of oxidative stress in 11 patients affected by histologically proven mitochondrial myopathy with progressive external ophthalmoplegia (PEO) and partial cytochrome c oxidase deficiency in muscle fibres. Six of the patients carried large-scale deletions of mitochondrial DNA. Biochemical assays included the determination of plasma and erythrocyte reduced glutathione (GSH) concentration, plasma malondialdehyde, fluorescent adducts of aldehydes with plasma proteins, and serum level of lipid peroxides. In patients with PEO the mean values of lipid peroxides and of the fluorescent adducts of aldehydes with plasma proteins were significantly higher with respect to normal controls, while the mean values of plasma and erythrocyte GSH concentration were significantly lower. The reported data indicate an increase of lipid peroxidation indexes along with the reduction of one of the most important antioxidant systems and suggest the hypothesis that overproduction of reduced oxygen species might be an adjunctive cause of cell damage in mitochondrial myopathies and encephalomyopathies associated with defects of oxidative phosphorylation.