ReviewOxidative stress induced-neurodegenerative diseases: the need for antioxidants that penetrate the blood brain barrier
Section snippets
Biosynthesis and effects of free radicals
A free radical is any chemical species that contains one or more unpaired electrons. Unpaired electrons alter the chemical reactivity of an atom or molecule, usually making it more reactive than the corresponding non-radical, because they act as electron acceptors and essentially “steal” electrons from other molecules. This loss of electrons is called oxidation, and free radicals are referred to as oxidizing agents because they tend to cause other molecules to donate their electrons (Halliwell
Antioxidants
Antioxidant defense mechanisms include: removal of O2, scavenging reactive oxygen/nitrogen species or their precursors, inhibition of ROS formation, binding of metal ions needed for the catalysis of ROS generation and up-regulation of endogenous antioxidant defenses. The protective efficacy of antioxidants depends on the type of ROS that is generated, the place of generation (body barriers such as the blood brain barrier reduce the permeability of most antioxidants) and the severity of the
Oxidative stress and excitatory amino acids
Although multiple factors can precipitate OS in cells, the neurotransmitter glutamate is the major effector of this process in the brain, primarily through activation of its ionotropic receptors. Glutamate and related excitatory amino acids account for most of the excitatory synaptic activity in the mammalian CNS and are released by an estimated 40% of all synapses. The ionotropic receptors can be distinguished by their pharmacological and electrophysiological properties: the
The blood brain barrier (BBB)
The brain needs a barrier that separates it from the blood, to permit the rigorous control of the brain microenvironment that is necessary for complex neural signaling. The blood brain barrier (BBB) is an endothelial barrier present in the capillaries that course through the brain (Reese and Karnovsky, 1967). According to ultrastructural studies, endothelial cells in brain differ fundamentally from those in most peripheral tissues, in two ways. First, they have very few endocytotic vesicles,
Antioxidants in the prevention and treatment of neurodegenerative disorders
The distribution of protective antioxidants in the brain has some interesting features. For instance, there is a relatively high concentration of the water-soluble antioxidant vitamin C in the brain. However, vitamin E concentrations are not remarkably different from those in other organs. The concentration of antioxidants varies within the different regions of the brain. For instance, the lowest concentration of vitamin E is found in the cerebellum (Vatassery, 1992). It has also been shown
Conclusions
Due to increased exposure to environmental damage, our endogenous antioxidant defense system is not completely effective. It seems reasonable to propose that antioxidants are very important in diminishing the cumulative effects of oxidative damage. Since OS has been implicated in the pathogenesis of many neurological, particularly neurodegenerative, diseases, antioxidants of widely varying chemical structures have been investigated for use as therapeutic agents. Most of the papers hereby
References (150)
- et al.
Involvement of free radicals in MPP+ neurotoxicity against rat dopaminergic neurons in culture
Neuroscience Letters
(1995) - et al.
Protective effects of grape seed proanthocyanids and selected antioxidants against TPA-induced hepatic and brain lipid peroxidation and DNA fragmentation, and peritoneal macrophage activation in mice
General Pharmacology
(1998) - et al.
Salen manganese complexes are superoxide dismutase mimics
Biochemical and Biophysical Research Commununications
(1993) Mitochondria, free radicals and neurodegeneration
Current Opinion in Neurobiology
(1996)- et al.
Tissue coenzyme Q (ubiquinone) and protein concentrations over the life span of the laboratory rat
Mechanisms of Aging and Development
(1985) - et al.
Antioxidant properties of melatonin — an emerging mystery
Biochemical Pharmacology
(1998) - et al.
Intracellular calcium as an index of neurotoxic damage
Toxicology
(1988) - et al.
Vitamin E attenuates the toxic effects of intrastriated injection of 6-hydroxydopamine (6-OHDA) in rats: behavioral and biochemical evidence
Brain Research
(1989) - et al.
The effects of glutathione glycoside in methyl mercury poisoning
Toxiciology and Applied Pharmacology
(1996) - et al.
Oxidative stress and antioxidant theory in Parkinson's disease
Progression in Neurobiology
(1996)