The effect of ascorbate and ubiquinone supplementation on plasma and CSF total antioxidant capacity

Studies in experimental traumatic brain injury (TBI) support a key role for oxidative stress. The degree of oxidative injury in clinical TBI, however, remains to be defined. We assessed antioxidant defenses and oxidative stress in pediatric TBI by applying a comprehensive battery of assays to cerebrospinal fluid samples. Using a protocol approved by our institutional review board, 87 cerebrospinal fluid samples from 11 infants and children with severe TBI (Glasgow Coma Scale score Յ8) and 8 controls were studied. Cerebrospinal fluid was drained as standard care after TBI. CSF was assessed on d 1, 2, and 5-7 after ventricular drain placement. Biochemical markers of oxidative stress included F 2 -isoprostane and protein sulfhydryl (detected by ELISA and fluorescence assay, respectively). Antioxidant defenses were measured by determination of total antioxidant reserve (via chemiluminescence assay), and ascorbate (via HPLC) and glutathione (via fluorescence assay) concentrations. Free radical production (ascorbate radical) was assessed by electron paramagnetic resonance spectroscopy. F 2 -isoprostane was markedly increased versus control, maximal on d 1 (93.8 Ϯ 30.8 pg/mL versus 7.6 Ϯ 5.1 pg/mL, p Ͻ 0.05). Total antioxidant reserve was reduced versus control. Reduction was maximal on Abbreviations TBI, traumatic brain injury CSF, cerebrospinal fluid EPR, electron paramagnetic resonance spectroscopy LMWA, low-molecular-weight antioxidants SOD, superoxide dismutase GSH, glutathione GCS, Glasgow Coma Scale AAPH, 2,2'-azobis(2-amidinopropane)dihydrochloride Trauma is the leading cause of death in children. Severe TBI is an important contributor to this mortality and to associated morbidity. TBI triggers a pathway of neuronal death involving loss of cellular calcium homeostasis, tissue acidosis, and oxidative stress (1). Data from experimental TBI support an important role for oxidative injury in early neuronal and vascular damage after TBI (2-5), as well as in secondary delete-

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“…4). The concentration of ascorbate in CSF obtained from control subjects was similar to that previously reported (36). (Fig.…”

Section: Antioxidant Status Of Csf After Tbisupporting

confidence: 77%

Assessment of Antioxidant Reserves and Oxidative Stress in Cerebrospinal Fluid after Severe Traumatic Brain Injury in Infants and Children

et al. 2002

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“…In a similar study, A␤ was found to prevent the oxidation of the lipoproteins from cerebral spinal fluid and plasma (12). Moreover, A␤ was shown to exhibit an antioxidant activity more effective than ascorbic acid in cerebral spinal fluid (20). The antioxidant activity of A␤ was also demonstrated in the decrease of cytoplasmic amounts of 8-hydroxyguanosine, a major product of nucleic acid oxidation present in elevated amounts in the brains of AD patients (21).…”

Section: Resultsmentioning

confidence: 73%

“…As metal ions are involved in the formation of amyloid plaques, the oxidative activity of metallo-A␤ derivatives against plasmid DNA was probed in vitro with gel electrophoresis. The oxidative activities of the Zn 2ϩ , Ni 2ϩ , and Cu 2ϩ complexes of A␤ [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] (ZnA␤ [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] , NiA␤ [1][2][3][4][5][6][7][8][9][10][11]…”

Section: Resultsmentioning

confidence: 99%

“…The metal binding was monitored through the changes in the NMR spectra. The peptides A␤ [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] and A␤ [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] and the paramagnetic shift reagent Co 2ϩ were prepared in d 6 -Me 2 SO. The metal ion was gradually titrated into the peptide, and the paramagnetically shifted 1 H NMR signals were detected.…”

Section: Methodsmentioning

confidence: 99%

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Catechol Oxidase-like Oxidation Chemistry of the 1–20 and 1–16 Fragments of Alzheimer's Disease-related β-Amyloid Peptide

Silva

Tay

2005

Journal of Biological Chemistry

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The Cu 2؉ complexes of the 1-16 and the 1-20 fragments of the Alzheimer's disease-related ␤-amyloid peptide (CuA␤) show significant oxidative activities toward a catechol-like substrate trihydroxylbenzene and plasmid DNA cleavage. The latter reflects possible oxidative stress to biological macromolecules, yielding supporting data to the pathological role of these soluble A␤ fragments. Abnormal metal-ion homeostasis has been closely associated with several neurodegenerative diseases, including Parkinson's, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease (i.e. human "mad cow" or prion disease), and Alzheimer's disease (AD) 1 (1-4). Because high cytoplasmic concentrations of free metal ions are toxic and potentially lethal, intricate physiological pathways have evolved to transport and distribute metal ions to their targets, which include enzymes and proteins (5). With aging, physiological processes responsible for accurate delivery of metal ions break down and "leakage" of free metal ions can cause toxic effects to cells (6, 7). Divalent ions of redox-active transition metals have often been associated with oxidative stress and closely involved in the chemistry of reactive oxygen species (ROS), including hydrogen peroxide as well as superoxide and hydroxyl radicals (8). Because increase in intracellular concentrations of metal ions is closely related to the effects of aging, oxidative stress, and AD, there is considerable interest in investigating the connection between malfunction of regulatory processes such as metal transport and the presence of ROS with the pathology of AD.The chemistry of redox-active metal complexes of ␤-amyloid peptide (A␤) has been an area of intense focus in the study of AD. The aggregation of A␤ within the neocortex is closely related to the pathology of AD and has been shown to be induced by metal binding (9, 10). The A␤ peptides are generated by the cleavage of the ubiquitous amyloid precursor protein by ␣, ␤, and ␥ secretases (11). A␤ in the form of insoluble plaques contains up to millimolar amounts of Zn 2ϩ , Cu 2ϩ , and Fe 3ϩ in the neocortical region of the brain (8); however, the cause/effect connection of the metallo-A␤ plaques with AD is still under debate (12). The metal coordination environment of the 1-40 and 1-42 peptides has been previously studied and their pH-dependent aggregation reported (10, 13). The results showed that the metal binding seemed to be non-stoichiometric with ϳ3.5 metal ions per pair of aggregated peptides and a cooperative binding pattern as the amount of aggregates increases (8). Because A␤ 1-42 and A␤ have been shown to bind Zn 2ϩ , Fe 3ϩ , and Cu 2ϩ with extremely low apparent dissociation constants by means of quantitative determination of the metal-complex precipitates (8), understanding of the metalbinding domain and its structure may shed light on the chemistry related to the neuropathology of AD.Although the coagulation of the peptide plaques leaves little doubt that interaction with cytoplasmic molecules is unlikely, smaller fragment...

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“…The concentrations and activities of these antioxidants may be important determinants of the IR-induced cerebral injury. The total antioxidant potential of CSF is substantially lower than that of plasma, and the major component of the potential in CSF seems to be ascorbic acid, 13 while in plasma it is uric acid. [11][12] It has been shown 14 that the plasma and cerebral tissue levels of some antioxidants are decreased during IR in animals, supposedly as a sign of increased oxidative stress.…”

mentioning

confidence: 99%

Low Plasma Antioxidant Activity Is Associated With High Lesion Volume and Neurological Impairment in Stroke

Leinonen

Ahonen²,

Lönnrot³

et al. 2000

Stroke

Self Cite

150

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Background and Purpose-Oxidative stress is probably involved in neuronal damage induced by ischemia-reperfusion.The purpose of this study was to assess the role of antioxidant activity in cerebral ischemic stroke. Methods-Antioxidant activity of blood plasma and cerebrospinal fluid was assessed in 22 patients with cerebral hemisphere infarction that was verified and quantified by MRI. Results-Low total peroxyl radical trapping potential of plasma, but not of cerebrospinal fluid, was associated with high lesion volume and high neurological impairment assessed by scores on NIH Stroke Scale, Barthel Index, and Hand Motor Score tests. The plasma concentrations of ascorbic acid, ␣-tocopherol, and protein thiols were also associated with the degree of neurological impairment. Conclusions-These data suggest that the antioxidant activity of plasma may be an important factor providing protection from neurological damage caused by stroke-associated oxidative stress. (Stroke. 2000;31:33-39.)

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The effect of ascorbate and ubiquinone supplementation on plasma and CSF total antioxidant capacity

Cited by 95 publications

References 22 publications

Assessment of Antioxidant Reserves and Oxidative Stress in Cerebrospinal Fluid after Severe Traumatic Brain Injury in Infants and Children

Assessment of Antioxidant Reserves and Oxidative Stress in Cerebrospinal Fluid after Severe Traumatic Brain Injury in Infants and Children

Catechol Oxidase-like Oxidation Chemistry of the 1–20 and 1–16 Fragments of Alzheimer's Disease-related β-Amyloid Peptide

Low Plasma Antioxidant Activity Is Associated With High Lesion Volume and Neurological Impairment in Stroke

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