title: Antioxidant activity of vitamin C in iron-overloaded human plasma.
abstract: Vitamin C (ascorbic acid, AA) can act as an antioxidant or a pro-oxidant in vitro, depending on the absence or the presence, respectively, of redox-active metal ions. Some adults with iron-overload and some premature infants have potentially redox-active, bleomycin-detectable iron (BDI) in their plasma. Thus, it has been hypothesized that the combination of AA and BDI causes oxidative damage in vivo. We found that plasma of preterm infants contains high levels of AA and F2-isoprostanes, stable lipid peroxidation end products. However, F2-isoprostane levels were not different between those infants with BDI (138 +/- 51 pg/ml, n = 19) and those without (126 +/- 41 pg/ml, n = 10), and the same was true for protein carbonyls, a marker of protein oxidation (0.77 +/- 0.31 and 0.68 +/- 0.13 nmol/mg protein, respectively). Incubation of BDI-containing plasma from preterm infants did not result in detectable lipid hydroperoxide formation (</=10 nM cholesteryl ester hydroperoxides) as long as AA concentrations remained high. Furthermore, when excess iron was added to adult plasma, BDI became detectable, and endogenous AA was rapidly oxidized. Despite this apparent interaction between excess iron and endogenous AA, there was no detectable lipid peroxidation as long as AA was present at >10% of its initial concentration. Finally, when iron was added to plasma devoid of AA, lipid hydroperoxides were formed immediately, whereas endogenous and exogenous AA delayed the onset of iron-induced lipid peroxidation in a dose-dependent manner. These findings demonstrate that in iron-overloaded plasma, AA acts an antioxidant toward lipids. Furthermore, our data do not support the hypothesis that the combination of high plasma concentrations of AA and BDI, or BDI alone, causes oxidative damage to lipids and proteins in vivo.
authors.affiliation: Joint Program in Neonatology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Berger
authors.forename: M C
authors.initials: MC
authors.lastname: Polidori
authors.forename: A
authors.initials: A
authors.lastname: Dabbagh
authors.forename: P J
authors.initials: PJ
authors.lastname: Evans
authors.forename: B
authors.initials: B
authors.lastname: Halliwell
authors.forename: J D
authors.initials: JD
authors.lastname: Morrow
authors.forename: L J
authors.initials: LJ
authors.lastname: Roberts
authors.forename: B
authors.initials: B
authors.lastname: Frei
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000378:metabolism*; D001205:Ascorbic Acid / Q000097:blood*; D001761:Bleomycin; D001798:Blood Proteins / Q000378:metabolism; D002788:Cholesterol Esters / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D007501:Iron / Q000097:blood*; D019190:Iron Overload / Q000097:blood*; D008055:Lipids / Q000097:blood; D010084:Oxidation-Reduction
chemical_list: D000975:Antioxidants; D001798:Blood Proteins; D002788:Cholesterol Esters; D008055:Lipids; D001761:Bleomycin; C081459:cholesteryl ester hydroperoxide; D007501:Iron; D001205:Ascorbic Acid