Dual effect of deferoxamine on free radical formation and reoxygenation injury in isolated hepatocytes
Caraceni, P.; Van Thiel, D.H.; Borle, A.B.
American Journal of Physiology 269(1 Pt 1): G132-G137
1995
ISSN/ISBN: 0002-9513 PMID: 7631791 Document Number: 450973
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- cntdot ) 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- cntdot 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- cntdot generation increased 11-fold, MDA increased 3.7-fold, and LDH release practically doubled. Low concentrations of DFO had no effect on O-2- cntdot generation but decreased MDA and LDH release from 44 to 75%. High concentrations of DFO significantly depressed O-2- cntdot 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- cntdot formation, and 2) at high concentrations, DFO acts as a nonspecific scavenger of oxygen free radicals such as O-2- cntdot .