Protective effect of allopurinol on hepatic energy metabolism in ischemic and reperfused rat liver.
Reactive oxygen species generated by xanthine oxidase during reperfusion of ischemic liver might in part be responsible for ischemic organ injury. In normothermic ischemia/reperfusion rat model, we investigated whether allopurinol pretreatment improved ischemia-induced mitochondrial dysfunction. Rats were subjected to 60 min of hepatic ischemia and to 1 h and 5 h of reperfusion thereafter. At 18 h and 1 h before ischemia, the animals received 0.25 mL of either saline or allopurinol (50 mg/kg) i.p. In saline-treated ischemic rats, serum aspartate aminotransferase levels increased significantly at 5 h (4685 +/- 310 IU/L) and were significantly reduced with allopurinol pretreatment. Similarly, mitochondrial lipid peroxidation was elevated in the saline-treated ischemic group, but this elevation was prevented by allopurinol. In contrast, mitochondrial glutamate dehydrogenase activity and ketone body ratio decreased in the saline-treated group, but this decrease was also inhibited by allopurinol. Hepatic ATP levels in the saline-treated rats were 42% lower 5 h after reperfusion. However, treatment with allopurinol resulted in significantly higher ATP levels. Allopurinol treatment preserved the concentration of AMP in ischemic liver but inhibited the accumulation of xanthine in reperfused liver. Our findings suggest allopurinol protects against mitochondrial injury, which prevents a mitochondrial oxidant stress and lipid peroxidation and preserves the hepatic energy metabolism.
Jeon
B R
BR
College of Pharmacy, Sungkyunkwan University, Suwon, South Korea.
Yeom
D H
DH
Lee
S M
SM
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood / Q000187:drug effects; D004734:Energy Metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005969:Glutamate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism*; D007659:Ketones / Q000097:blood; D015227:Lipid Peroxidation; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D007659:Ketones; D000493:Allopurinol; D014969:Xanthine Oxidase; D005969:Glutamate Dehydrogenase; D001219:Aspartate Aminotransferases