Free radicals, oxidative stress and oxidative damage in Parkinson's disease.

REPETTO, MARISA; DOMINGUEZ, RAUL; MARSCHOFF, ENRIQUE; SERRA, JORGE

Mechanisms in Parkinson's disease- Models and treatments

Intech

Lugar: Rijeka; Año: 2012; p. 57 - 78

Parkinson?s disease (PD) is an adult-onset disease of unknown etiology. Primary degeneration occurs in pigmented dopamine-containing neurons in the pars compacta of the substantia nigra with typical motor signs that appear with a loss of 60% of the dopaminergic neurons of the brain area. The actual physiopathology of PD remains uncertain, but there is evidence that oxidative stress participates in the neurodegeneration; neutrophils express a primary alteration of nitric oxide release in PD patients, where reactive oxygen species and oxidative stress parameters are more probably related to the evolution of PD. Peripheral markers of oxidative stress in red blood cells of neurological patients could be a reflection of the brain condition and suggests that oxygen free radicals are partially responsible of the damage observed in PD living patients (Serra, et al., 2001). Other reports suggest that mitochondrial dysfunction and impairment of the respiratory complexes are associated with the neuronal loss (Boveris & Navarro, 2008). The concept of oxidative stress is defined as an imbalance with increased oxidants or decreased antioxidants. The concept of oxidative stress as an imbalance situation implies that in the normal physiological condition there is a balance, or a controlled situation of quasi-equilibrium between oxidants and antioxidants. Oxidants are continually produced as secondary products of respiration and oxidative metabolism, and antioxidants are continually reacting with oxidant molecules. In the oxidative stress condition, oxidants increase or antioxidants decrease in a progressive and continuous form, sometimes including adaptive responses that involve the synthesis of antioxidants and antioxidant enzymes and that confer elasticity and reversibility to the biological situation of oxidative stress (Boveris et al., 2008). They defined the intracellular oxidative stress as a situation where increases of the steady-state concentrations of any intermediate produces an increase in oxidant intermediates, an increase in the chain reaction rate, and a decrease in intracellular antioxidants. Actually, the clinical evolution of patients with neurological diseases is based on psychological tests. The current hypotheses are that brain oxidative stress and damage are involved in the pathogenesis of neurodegenerative diseases such as Alzheimer?s and Parkinson?s diseases and non-neurodegenerative vascular dementia. The situation of oxidative stress evaluated by the peripheral markers of oxidative stress in the blood of neurological patients, seem to afford a reflection of the brain condition. Brain oxidative stress, with oxygen free radicals being responsible for brain damage, signals to peripheral blood, at least, through the diffusible products of lipid peroxidation. The peripheral markers provide a useful tool to determine the evolution of brain oxidative stress in neurological patients (Repetto, 2008).