Dual effect of deferoxamine on free radical formation and
reoxygenation injury in isolated hepatocytes.
Caraceni, Paolo, David H. Van Thiel, and Andre B. Borle.
Departments of Physiology and Surgery, University of Pittsburgh
School of Medicine, Pittsburgh, PA, 15261
APStracts 2:0046G, 1995.
The effects of low concentrations (10 and 100 [mu]M) and high
concentrations (1, 10 and 20 mM) of deferoxamine (DFO) on superoxide
(O2 x -) formation, lipid peroxidation and cell injury were studied
in freshly isolated perfused rat hepatocytes during a 2 h
reoxygenation period following 2 1/2 h of anoxia. O2 x - production
was measured by lucigenin-enhanced chemiluminescence, lipid
peroxidation by malondialdhyde (MDA) formation and cell injury by LDH
release. Upon reoxygenation and in the absence of DFO, O2 x -
generation increased 11 fold, MDA increased 3.7 fold and LDH release
practically doubled. Low concentrations of DFO had no effect on O2 x
- generation, but they decreased MDA and LDH release from 44 to 75%.
High concentrations of DFO significantly depressed O2 x - formation
with very little additional effect on MDA or LDH release. These
experiments illustrate in a biological system the dual action of DFO:
1) at low concentration, DFO acts as a specific iron chelator and
inhibits lipid peroxidation and cell injury without preventing O2 x -
formation; and 2) at high concentration, DFO acts as a non specific
scavenger of oxygen free radicals such as O2 x -.
Received 3 August 1994; accepted in final form 25 February 1995.
APS Manuscript Number G292-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 21 March 1995.