Oxidative stress is induced in female carriers of X-linked adrenoleukodystrophy.

ABSTRACT

X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disease biochemically characterized by the accumulation of very long chain fatty acids (VLCFA), particularly hexacosanoic (C260) and tetracosanoic acids (C240) in different tissues and in biological fluids and clinically characterized by central and peripheral demyelination and adrenal insufficiency. A considerable number of heterozygotes (HTZ) for X-ALD develop neurological symptoms like spinal cord involvement resembling milder forms of adrenomyeloneuropathy. However, the mechanisms of brain damage in hemizygotes and heterozygotes X-ALD individuals are poorly understood. Considering that oxidative stress was involved in various neurodegenerative disorders and that in a previous study we showed evidence that oxidative stress is probably involved in the pathophysiology of X-ALD symptomatic patients, in the present study we evaluated various oxidative stress parameters, namely thiobarbituric acid-reactive substances (TBA-RS), total antioxidant status (TAS) and total antioxidant reactivity (TAR) in plasma of HTZ individuals for X-ALD. It was observed that female carriers present a significant increase of TBA-RS measurement, indicating a stimulation of lipid peroxidation, as well as a decrease of TAR, reflecting a deficient capacity to rapidly handle an increase of reactive species. These results indicate that oxidative stress is involved in the pathophysiology of heterozygotes for X-ALD.