Different roles of radical scavengers - ascorbate and urate in the cerebrospinal fluid of amyotrophic lateral sclerosis patients

Abstract

Ferrous iron, released from iron deposits in the motor cortex and other brain regions of amyotrophic lateral sclerosis (ALS) patients, participates in the Fenton reaction in cerebrospinal fluid (CSF) alongside H2O2, which is continuously released by neuronal cells. In vivo, the production of notoriously reactive hydroxyl radicals via this reaction could lead to the progression of the disease. Herein, we have examined the effect of ascorbate and uric acid on the production of hydroxyl radicals in CSF from both sporadic ALS patients and control subjects. Electron paramagnetic resonance spectroscopy identified ascorbyl radicals in CSF from ALS patients whereas it was undetectable in control CSF. The addition of H2O2 to the CSF from ALS patients provoked further formation of ascorbyl radicals and the formation of hydroxyl radicals ex vivo. The hydroxyl addition of uric acid to CSF from ALS patients diminished the production of hydroxyl radicals. In conclusion, there are clear differences between the roles of the two examined radical scavengers in the CSF of ALS patients indicating that the use of ascorbate could have unfavourable effects in ALS patients.