title: Non-protein-bound transition metals and hydroxyl radical generation in cerebrospinal fluid of newborn infants with hypoxic ischemic encephalopathy.
abstract: Among various hypothetical mechanisms for the in vivo production of reactive oxygen species, transition metal-catalyzed reactions in cooperation with a biologic reducing agent like ascorbic acid or superoxide may be some of the most important. In the present study, we retrospectively examined the existence of non-protein-bound metal ions, an essentially hazardous pro-oxidant form of various transition metals, and the occurrence of metal-catalyzed reactive oxygen species production in cerebrospinal fluid (CSF) of 10 infants with hypoxic ischemic encephalopathy (HIE) subsequent to perinatal asphyxia and 12 control infants within 72 h of birth. Non-protein-bound iron was detected in eight out of 10 CSF samples from the HIE infants and its level was significantly correlated with Sarnat's clinical stage, whereas none of the control infants had detectable non-protein-bound iron levels. Non-protein-bound copper was below the detection limit in all CSF samples from both groups. Ascorbic acid was significantly increased in the CSF of HIE infants when compared with that of controls (means, 664.9 versus 449.4 microM, p = 0.008). ortho-Tyrosine and meta-tyrosine, which are highly specific and sensitive markers of protein oxidation induced by hydroxyl radicals, were significantly higher in HIE infants than in controls when evaluated by the ratio relative to their source amino acid, phenylalanine [means, 110.5 versus 75.4, p = 0.018 for ortho-tyrosine/phenylalanine; 104.6 versus 67.7 (nM/microM x 10(2)), p = 0.048 for meta-tyrosine/phenylalanine]. Both ratios were significantly correlated with non-protein-bound iron, but not with ascorbic acid. Our preliminary observations provide direct evidence that hydroxyl radicals are generated in the CNS during asphyxiation. Iron chelation therapy could be worth developing as a neuroprotective strategy for perinatal asphyxia.
authors.affiliation: Department of Pediatrics, Division of Neonatology, Osaka Medical College, Japan. ped025@poh.osaka-med.ac.jp
authors.forename: Tohru
authors.initials: T
authors.lastname: Ogihara
authors.forename: Kazuya
authors.initials: K
authors.lastname: Hirano
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ogihara
authors.forename: Kiryo
authors.initials: K
authors.lastname: Misaki
authors.forename: Mayo
authors.initials: M
authors.lastname: Hiroi
authors.forename: Takao
authors.initials: T
authors.lastname: Morinobu
authors.forename: Han-Suk
authors.initials: HS
authors.lastname: Kim
authors.forename: Satoru
authors.initials: S
authors.lastname: Ogawa
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Ban
authors.forename: Masashi
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tamai
mesh_terms: D000481:Allantoin / Q000134:cerebrospinal fluid; D001205:Ascorbic Acid / Q000134:cerebrospinal fluid; D015415:Biomarkers; D003300:Copper / Q000134:cerebrospinal fluid*; D003683:Dehydroascorbic Acid / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D017665:Hydroxyl Radical / Q000134:cerebrospinal fluid; D020925:Hypoxia-Ischemia, Brain / Q000134:cerebrospinal fluid*; D007231:Infant, Newborn; D007501:Iron / Q000134:cerebrospinal fluid*; D008297:Male; D018384:Oxidative Stress; D011485:Protein Binding; D017382:Reactive Oxygen Species / Q000134:cerebrospinal fluid
chemical_list: D015415:Biomarkers; D017382:Reactive Oxygen Species; D017665:Hydroxyl Radical; D000481:Allantoin; D003300:Copper; D007501:Iron; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid