title: Dual effect of deferoxamine on free radical formation and reoxygenation injury in isolated hepatocytes.
abstract: The effects of low concentrations (10 and 100 microM) and high concentrations (1, 10, and 20 mM) of deferoxamine (DFO) on superoxide (O2-.) formation, lipid peroxidation, and cell injury were studied in freshly isolated perfused rat hepatocytes during a 2-h reoxygenation period after 2.5 h of anoxia. O2-. production was measured by lucigenin-enhanced chemiluminescence, lipid peroxidation by malondialdehyde (MDA) formation, and cell injury by lactate dehydrogenase (LDH) release. On reoxygenation and in the absence of DFO, O2-. generation increased 11-fold, MDA increased 3.7-fold, and LDH release practically doubled. Low concentrations of DFO had no effect on O2-. generation but decreased MDA and LDH release from 44 to 75%. High concentrations of DFO significantly depressed O2-. formation, with very little additional effect on MDA or LDH release. These experiments illustrate in a biological system the dual effect of DFO: 1) at low Concentrations, DFO acts as a specific iron chelator and inhibits lipid peroxidation and cell injury without preventing O2-. formation, and 2) at high concentrations, DFO acts as a nonspecific scavenger of oxygen free radicals such as O2-.
authors.affiliation: Department of Physiology and Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.
authors.forename: P
authors.initials: P
authors.lastname: Caraceni
authors.forename: D H
authors.initials: DH
authors.lastname: Van Thiel
authors.forename: A B
authors.initials: AB
authors.lastname: Borle
mesh_terms: D000166:Acridines; D000332:Aerobiosis; D000693:Anaerobiosis; D000818:Animals; D002469:Cell Separation; D003676:Deferoxamine / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008163:Luminescent Measurements; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000166:Acridines; D017382:Reactive Oxygen Species; C033472:10,10'-dimethyl-9,9'-biacridinium; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D003676:Deferoxamine; D010100:Oxygen