IBIMOL   23987
Unidad Ejecutora - UE
capítulos de libros
Free radicals, oxidative stress and oxidative damage in Parkinson's disease.
Mechanisms in Parkinson's Disease - Models and Treatments
InTech - Open Access Publisher
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. Other reports suggest that mitochondrial dysfunction and impairment of the respiratory complexes are associated with the neuronal loss. 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. 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. 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. The peripheral markers of oxidative stress assayed were: a) Tert-butyl hydroperoxide initiated chemiluminescence (BOOH-CL): The increased of BOOH-CL values indicate the occurrence of oxidative stress in the membrane of the erythrocyte due to consume of the endogenous antioxidants; b) Plasma antioxidant capacity (TRAP): The decreased values of TRAP in plasma indicate that the reduction in the level of plasmatic hydrosoluble antioxidants (i.e., GSH, uric acid, ascorbic acid and bilirubin); c) Thiobarbituric acid reactive substances (TBARS): The increase in TBARS results from augmented levels of systemic and neuronal hydroperoxides that lead to an increment in lipid peroxidation; d) Cu-Zn superoxide dismutase (SOD): An increase in the activity of antioxidant enzyme SOD have has been regarded as markers of systemic oxidative stress, since the up-regulation of antioxidant enzyme expression was considered as an adaptive response to the oxidative stress situation. The data present here show that the pathologies evaluated are associated to oxidative stress. BOOH-CL was increased by 86% and TRAP values showed a decrease of 40% in Parkinson?s disease; also increases of 19% in TBARS, 55% in SOD and decrease by 28% in TRAP. The non-enzymatic antioxidants decrease their concentration during oxidative damage. A lower level of antioxidants as a consequence of a previous situation of oxidative damage will correspond to a higher BOOH-CL, TBARS and SOD. These three increases are indicative of the occurrence of systemic oxidative stress. Actually currently, the clinical evolution of patients with neurological diseases is evaluated by based on psychological tests. The clinical diagnostic of Parkinson?s disease patients (PD) is obtained accordingly realized in accord with the "United Kingdom Parkinson Disease Brain Bank Criteria". Patients were evaluated according to the Hoehn and Yahr´s scale in stages 1 to 3, and required a history of positive response to levodopa therapy. No patient presented vascular lesions on CT scanning. Present results prove that the BOOH-CL, TBARS, TRAP and SOD variables for determining oxidative stress and antioxidant status would be a useful tool for the biochemical and clinical evaluation of patients during the progression of the disease and clinical treatment. Moreover, the present results show linearity between pairs of oxidative stress variables and the ordering of the neurological patients´ diseases along the different regression lines pointing to the existence of an overall balance between oxidative insult, damage and protection. Close quantitative correspondences were found when TRAP and BOOH-CL were plotted against the Hoehn and Yahr´s scale in Parkinson patients. In pathological situations conditions the reactive oxygen species are generated and as a consequence of lipid peroxidation that may occur with (alpha-tocopherol deficiency. In addition to containing high concentrations of polyunsaturated fatty acids and transitional metals, red blood cells are constantly being subjected to various types of oxidative stress. However, red blood cells however are protected by a variety of antioxidant systems which are capable of preventing most of the adverse effects under normal conditions. Among the antioxidant systems in the red cells, (alpha-tocopherol possesses an important and unique role. (alfha-tocopherol may protect the red cells from oxidative damage via a free radical scavenging mechanism or as a structural component of the cell membranes. The increase of BOOH-CL and TBARS are indicative that alpha-tocopherol is the antioxidant consumed in erythrocytes and suggest that reactive oxygen species and lipid peroxidation catalyzed by reduced transition metals may be responsible for the onset of oxidative damage and the occurrence of systemic oxidative stress in PD. Accordingly, there is a statistically significant decrease in the measured TRAP, suggesting that an enhanced susceptibility of erythrocytes to the oxidative stress correlates with a decrease in its antioxidant defenses. These results indicate that BOOH-CL, TBARS, SOD and the TRAP evaluated by the present procedures could be a useful complementary measurement when assessing the oxidative stress condition in different clinical pathological situations.