Non protein bound iron as early predictive marker of neonatal brain damage

Buonocore, Giuseppe; Perrone, Serafina; Longini, Mariangela; Paffetti, Patrizia; Vezzosi, Piero; Gatti, Maria Gabriella; Bracci, Rodolfo

doi:10.1093/brain/awg116

Cited by 102 publications

(59 citation statements)

References 28 publications

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“…Previous studies reported a close association between an increased plasma concentration of NPBI within 8 h after birth and adverse outcomes of neonatal asphyxia. 10,24 Our study adds an important piece of information to the previous reports. It confirms the increased concentrations of NPBI in the CSF that correspond to its plasma concentrations; and it associates this abnormality to an increased level of MDA as a marker for lipid peroxidation in the CSF.…”

Section: Discussionsupporting

confidence: 54%

“…As shown in our study, TIBC was low and NPBI was detectable even in the plasma of healthy newborns at a concentration that was generally higher than reported at any other age. 10,24 Plasma concentrations of NPBI were further increased in the HIE group when compared to controls. Such finding is consistent with a number of studies that demonstrate iron delocalization in the setting of hypoxia, 25 ischemia reperfusion 26,27 and cardiac arrest.…”

Section: Discussionmentioning

confidence: 91%

“…33 Ferroxidase catalyzes the oxidation of ferrous iron to ferric iron, and this process is essential for ionic forms of iron to be incorporated into transferrin. The pro-oxidant NPBI has the ability to catalyze the formation of free radicals, (24) particularly at the neuronal compartment, which is rich in polyunsaturated fatty acids. 5 We demonstrated a significant link between NPBI and MDA concentrations in the CSF with short-term neurological outcome.…”

Section: Discussionmentioning

confidence: 99%

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Iron metabolism and lipid peroxidation products in infants with hypoxic ischemic encephalopathy

2008

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Background: Iron delocalization or misregulation of iron metabolism may play a critical role in the pathology of hypoxic ischemic encephalopathy (HIE).Objective: To study iron metabolism and lipid peroxidation in newborn infants and to correlate non-protein-bound iron (NPBI) concentration with the severity of the post-asphyxial injury and subsequent short-term outcomes.Study Design: Concentrations of NPBI and malondialdehyde (MDA) in the serum and in the cerebrospinal fluid (CSF) were measured in eight healthy newborn infants and nine newborn infants suffering from moderately severe HIE. Short-term outcomes (death, survival with or without neurological abnormality) were noted at hospital discharge.Result: Serum and CSF concentrations of both NPBI and MDA were significantly increased in HIE infants when compared to controls. Serum iron was significantly increased and total iron binding capacity was significantly decreased in HIE infants compared to controls. Out of the nine HIE infants, four infants died and two infants survived with abnormal neurological findings at hospital discharge. These six infants with clinical sequels had significantly increased concentrations of NPBI in the serum and in the CSF; and increased concentrations of MDA in the CSF when compared to the other three who survived without short-term abnormalities. Conclusion:We conclude that hypoxia ischemia alters iron metabolism and lipid peroxidation in newborn infants; and that NPBI and MDA in the CSF are increased in infants with HIE. This study supports a role for iron in oxidative injury to the central nervous system after hypoxic ischemic insults.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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Iron metabolism and lipid peroxidation products in infants with hypoxic ischemic encephalopathy

2008

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“…In the newborn period oxydative damage has been implicated in the pathogenesis of numerous diseases and entities, such as maternal preeclampsia (4), pre mature birth (5-7), asphyxia (8,9), neonatal respira tory distress syndrome (10)(11)(12), retinopathy (7,10).…”

Section: Oxidative Stress In Pediatric Diseasesmentioning

confidence: 99%

Diagnostic and Therapeutic Significance of the Oxidative Stress Parameters in Children

Bajcetic¹,

Brajovic²,

Korkut-Tešić³

2010

Journal of Medical Biochemistry

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Kratak sadr`aj: Farmakoterapija oboljenja kod dece predstavlja veliki izazov s obzirom da najve}i broj lekova koji se svakodnevno koristi nije pedijatrijski evalurian. Efikasnost terapije zavisi u velikoj meri od poznavanja patofiziolo{kih procesa u organizmu dece razli~itih uzrasta te istra`ivanja u tom pravcu predstavljaju imperativ. Naru{en balans u produkciji slobodnih kiseoni~kih/azotnih vrsta i parametara antioksidantne za{tite zna~ajan je patofiziolo{ki ~inilac brojnih oboljenja (npr. sr~ana insuficijencija, plu}na hiper tenzija, astma, neonatalna sepsa, karcinom i dr.) u razli~i tim de~ijim uzrastnim periodima. Reaktivne kiseoni ~ne/azot ne vrste imaju funkciju signalnih molekula u normal nim fiziolo{kim procesima. Njihova pove}ana produkcija mo`e izazvati o{te}enja koja mogu naru{iti normalne fiziolo{ke procese u }eliji i u krajnjem ishodu izazvati }elijsku smrt. U ovom radu dat je pregledni prikaz dosada{njih ispitivanja parametara oksidativnog stresa kod dece razli~ite starosne dobi za pojedina oboljenja. Tako|e, razmotrili smo sve potencijalne dijagnosti~ke i terapijske mogu}nosti parametara oksidativnog stesa u de~ijem uzrastu.Klju~ne re~i: parametri oksidativnog stresa, antioksidansi, deca.

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“…Protein CG content is the most widely used marker of oxidative modification of the proteins and the term carbonyl stress has been used to describe excess formation of CG under physiologic and pathologic conditions, such as hypoxia-induced NPBI (3)(4)(5)(6).…”

mentioning

confidence: 99%

Nonprotein-Bound Iron and Plasma Protein Oxidative Stress at Birth

et al. 2005

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We previously reported plasma nonprotein-bound iron (NPBI) as a reliable early indicator of intrauterine oxidative stress (OS) and brain injury. We tested the hypothesis that albumin, an NPBI serum carrier, is the major target of NPBIinduced OS. Twenty-four babies were randomly selected from 384 newborns constituting the final cohort of a prospective study undertaken to evaluate the predictive role of NPBI in cord blood for neurodevelopmental outcome. Twelve were selected in the group with lowest NPBI levels (0 -1.16 M) and good neurodevelopmental outcome and 12 in the group with highest NPBI levels (Ն15.2 M) and poor neurodevelopmental outcome. Protein carbonyl groups were identified in cord blood samples by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and Western blotting with anti-2,4-dinitrophenyl (DNP) antibodies. Two series of immunoreactive spots, corresponding to serum albumin and ␣-fetoprotein, were found only in the group with highest NPBI levels. We found an association between NPBI and carbonylated proteins in babies with highest NPBI levels. Since NPBI may produce hydroxyl radicals through the Fenton reaction, the major target of OS induced by NPBI is its carrier: albumin. Oxidation of albumin can be expected to decrease plasma antioxidant defenses and increase the likelihood of tissue damage due to OS in the newborns. Proteins are an important target for oxidative modification; oxidatively modified forms of proteins accumulate during OS induced by free radical (FR) generation. The modification is a consequence of oxidation of amino acid residues on proteins to form protein CG.CG form during normal aging (1) and in neonates receiving oxygen ventilation (2). Protein CG content is the most widely used marker of oxidative modification of the proteins and the term carbonyl stress has been used to describe excess formation of CG under physiologic and pathologic conditions, such as hypoxia-induced NPBI (3-6).NPBI indicate a low molecular mass iron form, free of high-affinity binding to transferrin, that seems to occur in plasma, complexed to citrate, lactate, or phosphate or loosely bound to albumin or other proteins (7). In blood, NPBI causes release of hydroxyl radical (OH·) by superoxide and hydrogen peroxide, possibly via iron-oxygen complexes (8). OH· is an extremely powerful oxidizing species. It attacks all classes of biologic macromolecules depolymerizing polysaccharides, breaking DNA strands, inactivating enzymes, and peroxidating lipids (9 -11). NPBI is released from hemoglobin when erythrocytes are challenged by an oxidative stress (12,13). The newborn is very susceptible to NPBI-induced oxidative stress (14). Recently we reported that NPBI released by erythrocytes in vitro is much higher with hypoxic erythrocytes from newborns compared with that from adults (6). Asphyxia could affect iron metabolism and lead to a significant increase in NPBI and lipid peroxidation in plasma of newborns with hypoxic ischemic encephalopathy, indicating that iron delocalization induced by asphyxia...

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Non protein bound iron as early predictive marker of neonatal brain damage

Cited by 102 publications

References 28 publications

Iron metabolism and lipid peroxidation products in infants with hypoxic ischemic encephalopathy

Iron metabolism and lipid peroxidation products in infants with hypoxic ischemic encephalopathy

Diagnostic and Therapeutic Significance of the Oxidative Stress Parameters in Children

Nonprotein-Bound Iron and Plasma Protein Oxidative Stress at Birth

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