Brain mitochondrial function and nitric oxide production after deprenil in vivo treatment.

CZERNICZYNIEC, A.; BUSTAMANTE, J.; LORES ARNAIZ, S.

Spetses Island, Greece

Otro; International Free Radical Summer School: Biomarkers of oxidative stress and responses.; 2006

Sociiety for Free Radical Research

Deprenyl is widely used for treatment of Parkinson’s disease because its antioxidant and neuroprotective effects. The aim of this study was to evaluate the effects of this drug on mitochondrial function and the involvement of nitric oxide (NO), through measurements of: (a) MAO activity, (b) NO production, (c) respiratory complex activities, (d) O2 consumption, (e) H2O2 production, (f) mitochondrial permeability transition (MPT) and (g) mitochondrial membrane potential. Fourteen months mice were injected i.p. with deprenyl (20 mg/kg) and sacrificed 1.5 hours after the administration. Monoamine oxidase activity was found 55% decreased in mitochondria from deprenyl-treated animals and as a consequence, H2O2 production was significantly decreased. Deprenyl inhibited NOS activity in cytosolic fractions and submitochondrial particles (SMP) by 40% and 55%, respectively. In similar conditions, SMP from deprenyl-treated animals showed increased cytochrome oxidase activity. A 51% increase in state 3 oxygen uptake was found after deprenyl treatment, but no significant changes were observed in state 4. Deprenyl treatment protected against calcium-induced depolarization and was able to inhibit calcium-induced MPT. This work provides evidence that deprenyl treatment may exert neuroprotective effects as an improvement of brain mitochondrial function, through a reduction of free radical production, prevention of calcium-induced MPT and maintaining a mitochondrial transmembrane potential.