Abstract
Background/Aims: Functional and morphological alterations of the hepatic sinusoidal endothelial cell
occur in several models of experimental liver injury and in clinical settings. The
causes of these alterations are multiple. The aim of this study was to test the hypothesis
that the early functional impairment and morphological alterations of the sinusoidal
endothelial cell and hepatic sinusoid associated with liver injury are mediated by
free radical species, such as superoxide anion and nitric oxide.
Methods: Isolated rat livers were perfused by recirculation with hemoglobin-free, Krebs-Henseleit
bicarbonate buffer and presented with a source of superoxide anion (xanthine oxidase+hypoxanthine)
or nitric oxide (S-nitroso-N-acetyl penicillamine). Hyaluronan uptake (an index of
sinusoidal endothelial cell scavenging function), thiobarbituric acid-reactive substances
content of the tissue (a marker of lipid peroxidation), reduced and oxidized glutathione
(a marker of the thiol system oxidation/reduction state), lactate dehydrogenase and
alanine aminotransferase activities (markers of cytolysis), as well as scanning and
transmission electron microscopic appearance of the sinusoid were evaluated.
Results: At the high concentrations used, both free radical generating systems suppressed
hyaluronan uptake, increased malondialdehyde content of the tissue, enhanced the release
of both liver enzymes, decreased the total glutathione content of the liver, and altered
the ratio of reduced/oxidized glutathione. Both free radical species induced dose-dependent
morphological alterations of the sinusoid, consisting of the appearance of large gaps
replacing the sieve-plated fenestration.
Conclusions: The free radical species-induced functional impairment and morphological alterations
of the liver sinusoid, presented in this study, closely resemble the early in vivo changes associated with liver injury under a variety of conditions, such as preservation
and reperfusion, or administration of hepatotoxicants such as D-galactosamine, Gram-negative
bacterial lipopolysaccharides, acetaminophen, alcohol and others. Therefore, we suggest
that early liver sinusoid injury, observed under these conditions, can be attributed
to the action of free radicals, such as superoxide anion and nitric oxide.
Keywords
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Article info
Publication history
Accepted:
August 31,
1998
Received in revised form:
August 24,
1998
Received:
May 12,
1998
Identification
Copyright
© 1999 Published by Elsevier Inc.
