DUAL EFFECT OF DEFEROXAMINE ON FREE-RADICAL FORMATION AND REOXYGENATION INJURY IN ISOLATED HEPATOCYTES

The effects of low concentrations (10 and 100 mu M) and high concentrations (1, 10, and 20 mM) of deferoxamine (DFO) on superoxide (O-2-radical anion) 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. O-2-radical-anion 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, O-2-radical-anion generation increased 11-fold, MDA increased 3.7-fold, and LDH release practically doubled. Low concentrations of DFO had no effect on O-2-radical-anion generation but decreased MDA and LDH release from 44 to 75%. High concentrations of DFO significantly depressed O-2-radical-anion 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 O-2-radical-anion formation, and 2) at high concentrations, DFO acts as a nonspecific scavenger of oxygen free radicals such as O-2-radical-anion.