Abstract
Toxins that pass through the blood-brain barrier put neurons and glia in peril. The damage inflicted is usually a consequence of the ability of these toxic agents to induce free radical generation within cells but especially at the level of the mitochondria. The elevated production of oxygen and nitrogen-based radicals and related non-radical products leads to the oxidation of essential macromolecules including lipids, proteins and DNA. The resultant damage is referred to as oxidative and nitrosative stress and, when the molecular destruction is sufficiently severe, it causes apoptosis or necrosis of neurons and glia. Loss of brain cells compromises the functions of the central nervous system expressed as motor, sensory and cognitive deficits and psychological alterations. In this survey we summarize the publications related to the following neurotoxins and the protective actions of melatonin: aminolevulinic acid, cyanide, domoic acid, kainic acid, metals, methamphetamine, polychlorinated biphenyls, rotenone, toluene and 6-hydroxydopamine. Given the potent direct free radical scavenging activities of melatonin and its metabolites, their ability to indirectly stimulate antioxidative enzymes and their efficacy in reducing electron leakage from mitochondria, it would be expected that these molecules would protect the brain from oxidative and nitrosative molecular mutilation. The studies summarized in this review indicate that this is indeed the case, an action that is obviously assisted by the fact that melatonin readily crosses the blood brain barrier.
Highlights
The brain, including the spinal cord, is a very highly metabolically active organ which, even at rest, utilizes an estimated 20% of the total oxygen taken up by the lungs
The findings reported in this beautifully-illustrated paper document that combining neural stem cells (NSCs) transplantation with melatonin treatment may improve outcome and, it could be a viable approach to use in the treatment of Parkinson disease
Co-administration of melatonin (5 mg/kg) attenuated the neural changes. While these findings suggest melatonin may be protective of the brain against Hg toxicity, a solid conclusion to this effect should not be based on the results of this single study
Summary
The brain, including the spinal cord, is a very highly metabolically active organ which, even at rest, utilizes an estimated 20% of the total oxygen taken up by the lungs. As important as oxygen is for the survival of neurons and glia, it indirectly contributes to their destruction and death over time The reason for this is that a small percentage (an estimated 1-4%) of the oxygen that enters cells is metabolized to derivatives that gradually erode and destroy essential molecules [30, 86, 148]. To combat free radical (ROS/RNS) destruction, all life forms have evolved an array of means to either quench radical generation, to convert radicals to metabolically nondestructive molecules, or to neutralize (scavenge) them immediately after they are formed This complex protective system which is designed to prevent radical-mediated organ malfunction, disease processes and aging is referred to as the antioxidative defensive system. The survey reviews the ability of the endogenously-produced antioxidant, melatonin, to battle against free radical damage and to protect the brain from molecular mutilation which would inevitably lead to motor and sensory disability, psychological disturbance and/or cognitive decline
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