Allopurinol plus pentoxifilline in hepatic ischaemia/reperfusion injury.
OBJECTIVE
Ischaemia/reperfusion injury of the liver is the major cause of liver dysfunction and cellular death in transplantation and in liver resection with hepatic pedicle clamping. Many agents are used to prevent this phenomenon, which occurs following interaction of different mediators during both ischaemia and reperfusion. In this study, we aimed to assess the effects of allopurinol, a xanthine oxidase inhibitor, and pentoxifilline, on liver ischaemia/reperfusion injury when used together and to compare these with the effects of using these agents singly.


METHODS
Thirty-two rats were divided into four groups consisting of eight rats: Group C, control; Group P, pentoxifilline; Group A, allopurinol; and Group PA, pentoxifilline + allopurinol. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels were measured before hepatic pedicle clamping, on the 45th minute of ischaemia and 15 and 45 minutes after reperfusion. Group P rats were injected with 50 mg/kg pentoxifilline, Group A rats 50 mg/kg allopurinol and Group PA rats were injected with both agents 15 minutes before hepatic pedicle clamping.


RESULTS
Ischaemia/reperfusion injury was produced by hepatic pedicle clamping, as demonstrated by AST, ALT and LDH increase. Injury prevention occurred in Groups P, A and PA. No significantly different (better) prevention was provided by giving allopurinol plus pentoxifilline to the rats. Furthermore, no difference was observed between the allopurinol and pentoxifilline injected groups in terms of preventing ischaemia/reperfusion injury.


CONCLUSIONS
Pretreatment with allopurinol or pentoxifilline resulted in significantly lower hepatic enzyme elevation than that in controls in the rat liver ischaemia/reperfusion model. Using both agents does not provide better protection than using either agent alone.
Yildirim
Sadik
S
Sişli Etfal Teaching State Hospital, Istanbul, Turkey. sadikyildirim@yahoo.com
Tok
Hasan
H
Köksal
Hakan
H
Erdem
Levent
L
Baykan
Adil
A
D000493:Allopurinol / Q000008:administration & dosage* / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use*; D007511:Ischemia / Q000517:prevention & control*; D008102:Liver Circulation / Q000187:drug effects*; D010431:Pentoxifylline / Q000008:administration & dosage* / Q000627:therapeutic use*; D051381:Rats; D015427:Reperfusion Injury / Q000517:prevention & control*
D004791:Enzyme Inhibitors; D000493:Allopurinol; D010431:Pentoxifylline