P. Caraceni et al., DUAL EFFECT OF DEFEROXAMINE ON FREE-RADICAL FORMATION AND REOXYGENATION INJURY IN ISOLATED HEPATOCYTES, American journal of physiology: Gastrointestinal and liver physiology, 32(1), 1995, pp. 132-137
The effects of low concentrations (10 and 100 mu M) and high concentra
tions (1, 10, and 20 mM) of deferoxamine (DFO) on superoxide (O-2-radi
cal anion) formation, lipid peroxidation, and cell injury were studied
in freshly isolated perfused rat hepatocytes during a 2-h reoxygenati
on period after 2.5 h of anoxia. O-2-radical-anion production was meas
ured by lucigenin-enhanced chemiluminescence, lipid peroxidation by ma
londialdehyde (MDA) formation, and cell injury by lactate dehydrogenas
e (LDH) release. On reoxygenation and in the absence of DFO, O-2-radic
al-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-rad
ical-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 prev
enting O-2-radical-anion formation, and 2) at high concentrations, DFO
acts as a nonspecific scavenger of oxygen free radicals such as O-2-r
adical-anion.