Inhibition of hypochlorous acid-mediated reactions by desferrioxamine. Implications for the mechanism of cellular injury by neutrophils.
Inhibition of free radical mechanisms by desferrioxamine, an iron chelator, is often thought to be a good indicator of iron-catalyzed hydroxyl radical (OH.) production. The specificity of desferrioxamine is critical for such identification. This study was undertaken to determine whether desferrioxamine could prevent the in vitro cytotoxic reactions of hypochlorous acid (HOCl), a major neutrophil-derived oxidant. Red blood cells were used as a target for HOCl, and cell lysis and haemoglobin oxidation were measured. Desferrioxamine, and its iron-chelated form, ferrioxamine, were shown to prevent both effects of HOCl. However, desferrioxamine was 6 to 8 times more efficient than either ferrioxamine or taurine, another amine which prevents HOCl-mediated cell lysis, in preventing both lysis and Hb oxidation. After reaction with HOCl, ferrioxamine and taurine retained almost all the oxidizing equivalents as long-lived chloramine. However, with desferrioxamine less than half the oxidizing equivalents were recovered as chloramines indicating that sites other than the terminal amine reacted with HOCl. The chloramines formed were able to oxidize molecules in solution, but being hydrophilic they were confined to the extracellular medium and cell lysis did not occur. The results indicate that scavenging of HOCl could be a factor in the inhibition by desferrioxamine of neutrophil-mediated cell lysis in vitro.
Vissers
M C
MC
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109.
Fantone
J C
JC
D002700:Chloramines / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000187:drug effects; D005609:Free Radicals; D006454:Hemoglobins / Q000378:metabolism; D006461:Hemolysis; D006801:Humans; D006997:Hypochlorous Acid / Q000037:antagonists & inhibitors*; D007501:Iron / Q000378:metabolism; D015394:Molecular Structure; D009504:Neutrophils / Q000502:physiology*
D002700:Chloramines; D005609:Free Radicals; D006454:Hemoglobins; D006997:Hypochlorous Acid; D007501:Iron; D003676:Deferoxamine