Post-hypoxic magnesium decreases nuclear oxidative damage in the fetal guinea pig brain

Maulik, Dev; Qayyum, Imran; Powell, Saul R.; Karantza, Maria; Mishra, Om P.; Delivoria‐Papadopoulos, Maria

doi:10.1016/s0006-8993(00)03153-x

Cited by 40 publications

(20 citation statements)

References 37 publications

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“…In the laboratory Although magnesium has been found to be protective against brain damage in limited experimental settings via diminished neuronal apoptosis, 47 decreased neuronal loss with imposed ischemia, 48,49 and reduced oxidative neuronal damage, 50,51 other studies have not shown any benefit. [52][53][54][55][56] In the laboratory, the research findings seem to differ according to the animal species used for experimentation, and the kind of artificial insult used to initiate the biological injury.…”

Section: Outcomes and Mechanismsmentioning

confidence: 99%

Brain lesions in newborns exposed to high-dose magnesium sulfate during preterm labor

Mittendorf

Dammann

2005

J Perinatol

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High-dosage, tocolytic magnesium sulfate (MgSO 4 ) administered to pregnant women during preterm labor can be toxic, and sometimes lethal, for their newborns (Cochrane Database of Systematic Reviews (relative mortality risk 2.82, 95% confidence interval 1.2-6.6)). Based on the results of the Magnesium and Neurologic Endpoints Trial and the work of many others, a unifying triangular concept is proposed to account for the increased prevalence of brain lesions, with their likely resultant mortality, in neonates and infants exposed to high-dose MgSO 4 in the context of preterm labor. We review the evidence that: (1) elevated circulating levels of serum ionized magnesium occurring in mothers, and therefore in their babies, at the time of delivery are associated with subsequent neonatal intraventricular hemorrhage (IVH); (2) neonatal IVH is strongly associated with lenticulostriate vasculopathy (LSV), an unusual mineralizing lesion involving the thalami and basal ganglia of the neonate; and, (3) exposure to 50 g or more of tocolytic MgSO 4 during preterm labor is associated with the development of LSV.

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Section: Outcomes and Mechanismsmentioning

confidence: 99%

Brain lesions in newborns exposed to high-dose magnesium sulfate during preterm labor

Mittendorf

Dammann

2005

J Perinatol

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“…Previous cytochemical studies also showed that low excellular Mg 2+ , [Mg 2+ ] e , affected the anti-oxidation ability of cells. In contrast, controlled studies have shown the protective characteristics that Mg supplementation displayed in cellular oxidative damage (Morrill et al 1998;Garcia et al 1998;Cernak et al 2000;Mak et al 2000;Manuel y Keenoy et al 2000;Maulik et al 2001). The evidence from these studies suggests that reactive oxygen species disorder induced by Mg-deficiency is involved in oxidative damage.…”

Section: Introductionmentioning

confidence: 99%

Magnesium Deficiency Enhances Hydrogen Peroxide Production and Oxidative Damage in Chick Embryo Hepatocyte In Vitro

Yang

Wu²,

Chen

et al. 2006

Biometals

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Magnesium deficiency and oxidative stress have been identified as correlative factors in many diseases. The origin of free radicals correlated with oxidative damage resulting from Mg-deficiency is unclear at the cellular level. To investigate whether hydrogen peroxide (H2O2) is associated in the oxidative stress induced by Mg-deficiency, the effect of Mg2+ deficiency (0, 0.4, 0.7 mM) on the metabolism of H2O2 was investigated in cultured chick embryo hepatocytes. After being cultured in the media with various concentrations of Mg2+ for 1, 2, 4, 6 and 10 days, parameters of H2O2 production, catalase activity, lipid peroxidation, intracellular total Mg and cell viability were analyzed. Results demonstrated that long-term incubation of chick embryo hepatocyte in extracellular Mg2+-deprivative and Mg2+-deficient (0.4 mM) states significantly enhanced the production of H2O2 (approximately twofold, respectively) and lipid peroxidation in the cell cultures, while decreasing the cell viability. Additionally, the reversing action of Mg2+ re-added to 1.0 mM and the partial reversing action of dimethylthiourea suggested that (i) [Mg2+]e deficiency induced the increase of H2O2 production, (ii) [Mg2+]e deficiency decreased catalase activity in chick embryo hepatocyte in vitro, subsequently causing oxidative stress and cell peroxidative damage.

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“…Increased intracellular Ca 2ϩ in turn activates proteases, phospholipases, and nitric oxide synthase (21,22). Activation of these enzymes results in the generation of oxygen free radicals, peroxidation of nuclear membrane lipids, and activation of endonucleases leading to fragmentation of nuclear DNA (22)(23)(24).…”

Section: Discussionmentioning

confidence: 99%

Effect of Moderate Hypocapnic Ventilation on Nuclear DNA Fragmentation and Energy Metabolism in the Cerebral Cortex of Newborn Piglets

et al. 2001

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Previous studies have shown that severe hypocapnic ventilation [arterial carbon dioxide partial pressure (PaCO 2 ) 7-10 mm Hg] in newborn animals results in decreased cerebral blood flow and decreased tissue oxidative metabolism. The present study tests the hypothesis that moderate hypocapnic ventilation (PaCO 2 20 mm Hg) will result in decreased cerebral oxidative metabolism and nuclear DNA fragmentation in the cerebral cortex of normoxemic newborn piglets. Studies were performed in 10 anesthetized newborn piglets. The animals were ventilated for 1 h to achieve a PaCO 2 of 20 mm Hg in the hypocapnic (H) group (n ϭ 5) and a PaCO 2 of 40 mm Hg in the normocapnic, control (C) group (n ϭ 5). Tissue oxidative metabolism, reflecting tissue oxygenation, was documented biochemically by measuring tissue ATP and phosphocreatine (PCr) levels. Cerebral cortical nuclei were purified, nuclear DNA was isolated, and DNA content was determined. DNA samples were separated, stained, and compared with a standard DNA ladder. Tissue PCr levels were significantly lower in the H group than the C group (2.32 Ϯ 0.66 versus 3.73 Ϯ 0.32 mol/g brain, p Ͻ 0.05), but ATP levels were preserved. Unlike C samples, H samples displayed a smear pattern of small molecular weight fragments between 100 and 12,000 bp. The density of DNA fragments was eight times higher in the H group than the C group, and DNA fragmentation varied inversely with levels of PCr (r ϭ 0.93). These data demonstrate that moderate hypocapnia of 1 h duration results in decreased oxidative metabolism that is associated with DNA fragmentation in the cerebral cortex of newborn piglets. We speculate that hypocapnia-induced hypoxia results in increased intranuclear Ca 2ϩ flux, which causes protease and endonuclease activation, DNA fragmentation, and periventricular leukomalacia in newborn infants. Preterm and ill term infants are at risk for brain injury, subsequent neurodevelopmental delay, and CP, partially because of alterations in CBF (1). In neonates, white matter ischemia often results in ultrasonographic evidence of PVL, which has been associated with the development of CP in human infants (2).Brain ischemia has been associated with hypocapnia owing to the effect of pH and CO 2 on cerebral vascular tone (3). In multiple studies both the degree and duration of hypocapnia have been associated with an increased incidence of PVL and CP in preterm infants (4 -6). In one study of 251 infants Ͻ34 wk gestation, 50% of ventilated preterm infants with a PaCO 2 Ͻ17 mm Hg at least once during the first 3 d of life, and 30% of those with PaCO 2 of 7-20 mm Hg, developed CP or PVL or both (6). In a study of 26 ventilated preterm infants Ͻ1500 g, 23% of infants with PaCO 2 values Ͻ20 mm Hg during the first 24 h of life developed cystic PVL compared with 6% of infants who had normal PaCO 2 values during the same period (7). In another study of 103 preterm infants, the duration of hypocapnia (defined as a PaCO 2 Յ30 mm Hg) during the first 72 h of life was an independent predictor of PVL and ...

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Post-hypoxic magnesium decreases nuclear oxidative damage in the fetal guinea pig brain

Cited by 40 publications

References 37 publications

Brain lesions in newborns exposed to high-dose magnesium sulfate during preterm labor

Brain lesions in newborns exposed to high-dose magnesium sulfate during preterm labor

Magnesium Deficiency Enhances Hydrogen Peroxide Production and Oxidative Damage in Chick Embryo Hepatocyte In Vitro

Effect of Moderate Hypocapnic Ventilation on Nuclear DNA Fragmentation and Energy Metabolism in the Cerebral Cortex of Newborn Piglets

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