The effects of allopurinol in hepatic ischemia and reperfusion: experimental study in rats.
OBJECTIVE
Some studies have shown that postischemic hepatic dysfunction is mainly due to oxygen free radicals that are generated by xanthine oxidase. The present study was undertaken to determine the effect of allopurinol, an inhibitor of xanthine oxidase, on oxidative stress, liver injury and histologic alterations induced by hepatic ischemia-reperfusion in rats.


METHODS
One hundred and sixty Wistar rats were used and divided into three groups. Group 1: sham operation; group 2: 50 min of ischemia followed by 1 h of reperfusion, and group 3: pretreatment with allopurinol and 50 min of ischemia followed by 1 h of reperfusion. The effect of allopurinol was evaluated by plasma levels of alanine aminotransferase and aspartate aminotransferase, histopathologic studies, and lipid peroxidation measured by the thiobarbituric acid reactive substances method and chemiluminescence initiated by tert-butyl hydroperoxide technique.


RESULTS
Ischemia followed by reperfusion promoted an increase in lipid peroxidation of the hepatic cells when compared to the sham-operated group (p<0.05). This increase was attenuated in the group treated with allopurinol (p< 0.05). Allopurinol also showed a protective effect on hepatocellular necrosis (p<0.05), and the plasma levels of liver enzymes returned earlier to the normal range in rats pretreated with allopurinol in comparison to those that did not receive the drug (p<0.05).


CONCLUSIONS
Allopurinol exerted a protective effect on hepatic ischemia and reperfusion in rats. The administration of this drug prior to liver operations should be considered to be submitted to trials in humans.
Rhoden
E
E
Course of Post-Graduation in Medical Clinic of the Clinical Hospital of Porto Alegre, Porto Alegre, Brazil.
Pereira-Lima
L
L
Lucas
M
M
Mauri
M
M
Rhoden
C
C
Pereira-Lima
J C
JC
Zettler
C
C
Petteffi
L
L
Belló-Klein
A
A
D000410:Alanine Transaminase / Q000097:blood; D000493:Allopurinol / Q000627:therapeutic use*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D007511:Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008102:Liver Circulation; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D013997:Time Factors
D004791:Enzyme Inhibitors; D008054:Lipid Peroxides; D000493:Allopurinol; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase