Ascorbyl radical formation in patients with sepsis: effect of ascorbate loading.
Patients with sepsis have low concentrations of antioxidants, including ascorbic acid, and also have increased concentrations of markers of free radical damage. Although ascorbic acid is a potent antioxidant, it can act as a prooxidant by promoting iron-catalysed reactions. We measured baseline total vitamin C and bleomycin-detectable "free" iron levels and ascorbyl radical concentrations before and after intravenous infusion of 1 g ascorbic acid in patients with sepsis and healthy control subjects. Vitamin C concentrations were decreased in patients compared to healthy subjects (p < 0.0001), and "free" iron was increased (p < 0.002). Preinfusion ascorbyl radical concentrations were not different in patients and controls. Postinfusion ascorbyl radical levels increased in both controls and patients, with larger increases in healthy subjects (p < 0.0001), suggesting suboptimal basal vitamin C levels and increased scavenging of a constant oxidant pool by ascorbate in the controls. In the patients, who were all vitamin C deficient, infused ascorbate was rapidly consumed, either via the promotion of redox cycling of iron or as a result of radical scavenging. This study demonstrates markedly different handling of infused ascorbate in patients with sepsis and healthy subjects, and further studies are needed to elucidate the relative anti- and pro-antioxidant mechanisms of ascorbate in patients with raised "free" iron levels.
Academic Unit of Anaesthesia & Intensive Care, University of Aberdeen, UK.
H F
HF
Galley
M J
MJ
Davies
N R
NR
Webster
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000097:blood / Q000494:pharmacology*; D016227:Benzoquinones / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D001761:Bleomycin / Q000378:metabolism; D003497:Cyclic N-Oxides; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D005609:Free Radicals / Q000032:analysis / Q000097:blood / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000097:blood / Q000378:metabolism; D008297:Male; D009589:Nitrogen Oxides / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy / Q000378:metabolism*; D013113:Spin Labels
D000900:Anti-Bacterial Agents; D000975:Antioxidants; D016227:Benzoquinones; D003497:Cyclic N-Oxides; D005609:Free Radicals; D009589:Nitrogen Oxides; D013113:Spin Labels; D001761:Bleomycin; C025232:semiquinone radicals; C029217:phenyl-N-tert-butylnitrone; D007501:Iron; D001205:Ascorbic Acid