Postischemic tissue injury by iron-mediated free radical lipid peroxidation

White, Blaine C.; Krause, Gary S.; Aust, Steven D.; Eyster, George E.

doi:10.1016/s0196-0644(85)80062-7

Cited by 81 publications

(18 citation statements)

References 37 publications

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“…Fe 2+ is released from surrounding cells and iron-binding proteins during transient focal ischemia. The released Fe 2+ can also convert hydrogen peroxide to hydroxyl radical, and may mediate lipid peroxidation during reperfusion (White et al, 1985;Zaleska and Floyd, 1985). Late-onset iron deposition was also observed after transient focal ischemia in rat brain (Kondo et al, 1995).…”

Section: Production Of Reactive Oxygen Species By Transition Metalsmentioning

confidence: 96%

Cellular and Molecular Pathways of Ischemic Neuronal Death

Won¹,

Kim²,

Gwag³

2002

BMB Reports

201

172

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Three routes have been identified triggering neuronal death under physiological and pathological conditions. Excess activation of ionotropic glutamate receptors cause influx and accumulation of Ca 2+ and Na + that result in rapid swelling and subsequent neuronal death within a few hours. The second route is caused by oxidative stress due to accumulation of reactive oxygen and nitrogen species. Apoptosis or programmed cell death that often occurs during developmental process has been coined as additional route to pathological neuronal death in the mature nervous system. Evidence is being accumulated that excitotoxicity, oxidative stress, and apoptosis propagate through distinctive and mutually exclusive signal transduction pathway and contribute to neuronal loss following hypoxic-ischemic brain injury. Thus, the therapeutic intervention of hypoxic-ischemic neuronal injury should be aimed to prevent excitotoxicity, oxidative stress, and apoptosis in a concerted way.

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Section: Production Of Reactive Oxygen Species By Transition Metalsmentioning

confidence: 96%

Cellular and Molecular Pathways of Ischemic Neuronal Death

Won¹,

Kim²,

Gwag³

2002

BMB Reports

201

172

View full text Add to dashboard Cite

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“…Under these pathological conditions, iron released from ironbinding proteins such as ferritin and cytochromes can catalyze free radical reactions by Fenton chemistry and Haber-Weiss cycle, resulting in damage to all types of biomolecules [24,31,39]. In fact, lipid, DNA, and protein oxidation by iron-catalyzed reactive-oxygen species (ROS) such as hydroxyl radicals and peroxyl/alkoxyl radicals is evident by elevated levels of malondialdehyde, 4-hydroxynonenal, isoprostanes, 8-hydroxyguanine in the blood and/or brain in AD, PD, and stroke [1,7,34,36,58].…”

Section: Introductionmentioning

confidence: 99%

Blood-derived iron mediates free radical production and neuronal death in the hippocampal CA1 area following transient forebrain ischemia in rat

et al. 2010

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Abnormal brain iron homeostasis has been proposed as a pathological event leading to oxidative stress and neuronal injury under pathological conditions. We examined the possibility that neuronal iron overload would mediate free radical production and delayed neuronal death (DND) in hippocampal CA1 area after transient forebrain ischemia (TFI). Mitochondrial free radicals (MFR) were biphasically generated in CA1 neurons 0.5-8 and 48-60 h after TFI. Treatment with Neu2000, a potent spin trapping molecule, as well as trolox, a vitamin E analogue, blocked the biphasic MFR production and attenuated DND in the CA1, regardless of whether it was administered immediately or even 24 h after reperfusion. The late increase in MFR was accompanied by iron accumulation and blocked by the administration of deferoxamine-an iron chelator. Iron accumulation was attributable to prolonged upregulation of the transferrin receptor and to increased uptake of peripheral iron through a leaky blood-brain barrier. Infiltration of ironcontaining cells and iron accumulation were attenuated by depletion of circulating blood cells through X-ray irradiation of the whole body except the head. The present findings suggest that excessive iron transported from blood mediates slowly evolving oxidative stress and neuronal death in CA1 after TFI, and that targeting ironmediated oxidative stress holds extended therapeutic time window against an ischemic event.

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“…Concerns have been raised about the administration of ascorbic acid in the presence of redoxactive transition metal ions, since ascorbate can reduce transition metal ions and catalyse the Fenton-driven generation of hydroxyl and alkoxyl radicals in vitro [13]. Although the thermodynamics of this reaction in vivo remain controversial [14], an acute bout of physical exercise has been shown to liberate extracellular 'catalytic' iron [15] that, in the presence of supplementary ascorbic acid, may potentially compound the generation of ROS [16].…”

Section: Introductionmentioning

confidence: 99%

Molecular detection of exercise-induced free radicals following ascorbate prophylaxis in type 1 diabetes mellitus: a randomised controlled trial

et al. 2008

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Aims/hypothesis Patients with type 1 diabetes mellitus are more susceptible than healthy individuals to exercise-induced oxidative stress and vascular endothelial dysfunction, which has important implications for the progression of disease. Thus, in the present study, we designed a randomised doubleblind, placebo-controlled trial to test the original hypothesis that oral prophylaxis with vitamin C attenuates rest and exercise-induced free radical-mediated lipid peroxidation in type 1 diabetes mellitus. Methods All data were collected from hospitalised diabetic patients. The electron paramagnetic resonance spectroscopic detection of spin-trapped α-phenyl-tert-butylnitrone (PBN) adducts was combined with the use of supporting markers of lipid peroxidation and non-enzymatic antioxidants to assess exercise-induced oxidative stress in male patients with type 1 diabetes (HbA 1c 7.9±1%, n=12) and healthy controls (HbA 1c 4.6±0.5%, n=14). Following participant randomisation using numbers in a sealed envelope, venous blood samples were obtained at rest, after a maximal exercise challenge and before and 2 h after oral ingestion of 1 g ascorbate or placebo. Participants and lead investigators were blinded to the administration of either placebo or ascorbate treatments. Primary outcome was the difference in changes in free radicals following ascorbate ingestion. Results Six diabetic patients and seven healthy control participants were randomised to each of the placebo and ascorbate groups. Diabetic patients (n=12) exhibited an elevated concentration of PBN adducts (p<0.05 vs healthy, n=14), which were confirmed as secondary, lipid-derived oxygen-centred alkoxyl (RO·) radicals (a nitrogen =1.37 mT and aβ hydrogen =0.18 mT). Lipid hydroperoxides were also selectively elevated and associated with a depression of retinol and lycopene (p<0.05 vs healthy). Vitamin C supplementation increased plasma vitamin C concentration to a similar degree in both groups (p<0.05 vs presupplementation) and attenuated the exercise-induced oxidative stress response (p<0.05 vs healthy).There were no selective treatment differences between groups in the primary outcome variable. Conclusions/interpretation These findings are the first to suggest that oral vitamin C supplementation provides an Diabetologia

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Postischemic tissue injury by iron-mediated free radical lipid peroxidation

Cited by 81 publications

References 37 publications

Cellular and Molecular Pathways of Ischemic Neuronal Death

Cellular and Molecular Pathways of Ischemic Neuronal Death

Blood-derived iron mediates free radical production and neuronal death in the hippocampal CA1 area following transient forebrain ischemia in rat

Molecular detection of exercise-induced free radicals following ascorbate prophylaxis in type 1 diabetes mellitus: a randomised controlled trial

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