Oxidative damage in the central nervous system: protection by melatonin

Reíter, Russel J.

doi:10.1016/s0301-0082(98)00052-5

Cited by 802 publications

(694 citation statements)

References 222 publications

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“…The brain is particularly vulnerable to oxidative injury because of its high rate of oxygen consumption, intense production of reactive radicals, and high levels of transition metals, such as iron that catalyze the production of reactive radicals. Moreover, neuronal membranes are rich in PUFA that are a source of LPO reaction [30]. Establishing the time course of oxidative stress provides information on a possible therapeutic window for protection against oxidative and/or nitrosative insults in the hippocampus.…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress and modification of synaptic proteins in hippocampus after traumatic brain injury

Ansari

Roberts

Scheff

2008

Free Radical Biology and Medicine

277

220

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Oxidative stress, an imbalance between oxidants and antioxidants, contributes to the pathogenesis of traumatic brain injury (TBI). Oxidative neurodegeneration is a key mediator of exacerbated morphological responses and deficits in behavioral recoveries. The present study assessed early hippocampal sequential imbalance to possibly enhance antioxidant therapy. Young adult male Sprague-Dawley rats were subjected to a unilateral moderate cortical contusion. At various times post TBI, animals were killed and the hippocampus analyzed for antioxidants (GSH, GSSG, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, glucose-6-phosphate dehydrogenase, superoxide dismutase and catalase), and oxidants (acrolein,, protein carbonyl [PC] and 3-nitrotyrosine. Synaptic markers (synapsin-I, post synaptic density-95 [PSD-95], synapse associated protein-97 [SAP-97], growth associated protein-43 were also analyzed. All values were compared to sham operated animals. Significant time-dependent changes in antioxidants were observed as early as 3 h post trauma and paralleled increases in oxidants (4-HNE, acrolein and PC) with peak values obtained at 24-48 h. Time dependent changes in synaptic proteins (synapsin-I, PSD-95 and SAP-97) occurred well after levels of oxidants peaked. These results indicate that depletion of antioxidant systems following trauma could adversely affect synaptic function and plasticity. Early onset of oxidative stress suggests that the initial therapeutic window following TBI appears to be relatively short and it may be necessary to stagger selective types of anti-oxidant therapy to target specific oxidative components.

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Section: Discussionmentioning

confidence: 99%

Oxidative stress and modification of synaptic proteins in hippocampus after traumatic brain injury

Ansari

Roberts

Scheff

2008

Free Radical Biology and Medicine

277

220

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“…Protection by melatonin in other models of neurotoxicity, including hyperbaric hyperoxia-exposed rats, cyanide-induced seizures in rats, and damino-levulinic acid-induced neuronal damage in rat brain homogenates, was also provided [Reiter et al, 1997aReiter, 1998]. In experimental models of sepsis induced by administration of lipopolysaccharide (LPS) to rats, melatonin administration reportedly counteracted most of the markers of cell injury, including the inhibition of iNOS expression and subsequent NO production Crespo et al, 1999].…”

Section: Melatonin and Ros And Rnsmentioning

confidence: 99%

“…In different models of aging, including a relative melatonin deficiency, and in age-related diseases, such as cancer and cataracts, melatonin administration has been shown to be protective Reiter, 1999]. The fact that melatonin decreases with age has been suggest as contributing to aging in mammals [Reiter, 1998].…”

Section: Melatonin and Ros And Rnsmentioning

confidence: 99%

Melatonin, mitochondria, and cellular bioenergetics

Acuña-Castroviejo

Martı́n

Macías

et al. 2001

Journal of Pineal Research

Self Cite

383

313

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Aerobic cells use oxygen for the production of 90-95% of the total amount of ATP that they use. This amounts to about 40 kg ATP/day in an adult human. The synthesis of ATP via the mitochondrial respiratory chain is the result of electron transport across the electron transport chain coupled to oxidative phosphorylation. Although ideally all the oxygen should be reduced to water by a four-electron reduction reaction driven by the cytochrome oxidase, under normal conditions a small percentage of oxygen may be reduced by one, two, or three electrons only, yielding superoxide anion, hydrogen peroxide, and the hydroxyl radical, respectively. The main radical produced by mitochondria is superoxide anion and the intramitochondrial antioxidant systems should scavenge this radical to avoid oxidative damage, which leads to impaired ATP production.

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“…This agent can reduce the extent of injury to the CNS caused by a wide range of neurotoxicants including iron-induced necrosis [25], mercury [30], kainate [28], cyanide [52] and paraquat [29]. Melatonin levels decrease with age [33]. Since melatonin can prolong survival time of mice [2,31] albeit associated with increased spontaneous tumor incidence according to one report [2] -this is likely to be relevant to the aging process [36], even if the exact mechanism is incompletely understood [54].…”

Section: Introductionmentioning

confidence: 99%

Dietary melatonin selectively reverses age-related changes in cortical cytokine mRNA levels, and their responses to an inflammatory stimulus

Sharman

Yang

et al. 2002

Neurobiology of Aging

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The basal levels of expression of mRNA of cytokines, interleukin-6 (IL-6) and tumor necrosis factor (TNF-␣), in the cerebral cortex of 5 and 26 month-old male B6C3F1 mice have been compared. In addition, the responsivity of animals of differing age to an inflammatory stimulus (lipopolysaccharide, LPS) has been studied. Basal levels of both of these cytokine mRNAs were elevated in aged animals relative to the younger group. However LPS administration led to a robust increase in cytokine mRNA levels in the younger animals but in aged mice, there was either an unchanged (IL-6) or a depressed (TNF-␣) response. Administration of dietary melatonin (200 ppm) to aged mice for 6 weeks prior to sacrifice, resulted in reduction of basal levels of cytokine mRNA to values found in the younger animals. Furthermore, following administration of LPS to melatonin fed animals, cerebral cytokine mRNA levels were significantly elevated rather than being unchanged or depressed. Taken together these findings reflect a trend in the cortices of melatonin-treated aged mice, to more closely approximate the status of younger mice. For comparative purposes, parallel studies were carried out using an immunologically active organ (spleen) and a non-neural organ with a low rate of cell turnover (heart muscle). In both these tissues, basal levels of cytokine mRNAs of animals of either age were very low, and there was a marked positive response to LPS. Dietary melatonin had no effect on the responses of TNF-␣ mRNA to LPS but attenuated the reaction of splenic IL-6 mRNA, thus bringing the response closer to that of the younger mice.

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Oxidative damage in the central nervous system: protection by melatonin

Cited by 802 publications

References 222 publications

Oxidative stress and modification of synaptic proteins in hippocampus after traumatic brain injury

Oxidative stress and modification of synaptic proteins in hippocampus after traumatic brain injury

Melatonin, mitochondria, and cellular bioenergetics

Dietary melatonin selectively reverses age-related changes in cortical cytokine mRNA levels, and their responses to an inflammatory stimulus

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