Free radical scavengers improve liver function but not morphological changes induced by reperfusion injury.
OBJECTIVE
Reperfusion injury (RI) is associated with high generation of reactive oxygen species (ROS), but the extent of involvement of these agents in the injury remains controversial. The present study aimed to examine the effectiveness of ROS scavengers against hepatic reperfusion injury in the rat.


METHODS
The RI was induced in the liver using an isolated slow-flow, reflow perfused rat liver in both anterograde and retrograde perfusion. The effects of gentisic acid, N-acetyl cysteine, and trolox C on the superoxide production, liver function, and morphological changes were examined using different biochemical and histological assays.


RESULTS
The hepatic RI caused a significant (p < 0.05) increase in superoxide production and enzyme releases and a decrease in bile flow in both directions. Histological changes induced by RI include apoptosis, necrosis, pale cytoplasm, cell vacuolation, and attenuation of cell cords. Although the production of superoxide in retrograde direction was significantly less than the anterograde, the extent of the injury in the retrograde was greater than the anterograde direction. Pretreatment of the livers with each of the test compounds significantly reduced the release of lactate dehydrogenase and aspartate aminotransferase and improved bile flow in the liver exposed to hypoxia/reperfusion. However, they failed to protect the liver against the structural alterations induced by RI.


CONCLUSIONS
ROS scavengers can reduce superoxide-induced damage and improve the liver function, but they are not able to prevent the structural changes. It shows that ROS are not the sole causative mechanism of hepatic RI and other mechanisms and mediators may be involved.
1Faculty of Veterinary Medicine, University of Tehran , Tehran , Iran.
Hossein-Ali
HA
Arab
Neal I
NI
Walker
Kee
K
Cheung
Peter E
PE
Hickman
Jolia M
JM
Potter
Mehri
M
Kadkhodaee
Michael S
MS
Roberts
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002839:Chromans / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005841:Gentisates / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D015427:Reperfusion Injury / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology*; D013481:Superoxides / Q000378:metabolism
D002839:Chromans; D016166:Free Radical Scavengers; D005841:Gentisates; D013481:Superoxides; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; C010925:2,5-dihydroxybenzoic acid; D000111:Acetylcysteine
anterograde and retrograde perfusion; free radical scavengers; hypoxia/reperfusion; isolated perfused rat liver; superoxide