Dual effect of deferoxamine on free radical formation and reoxygenation injury in isolated hepatocytes

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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-.

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