ALLOPURINOL EFFECTS IN RAT-LIVER TRANSPLANTATION ON RECOVERY OF ENERGY-METABOLISM AND FREE RADICAL-INDUCED DAMAGE

Rat livers were orthotopically transplanted after 90-min cold ischemia (group 1) or after 20-min warm and 70-min cold ischemia without (group 2) or with (group 3) allopurinol treatment (AT) (50 mg/kg i.v. 10 min prior to warm ischemia into the donor, flush perfusates with 1 mmol/l). Recovery processes were followed up for 60 min of reperfusion. Liver tissue levels of ATP and total adenine nucleotides were restored in group 1 to almost preischemic ranges within 15-30 min, remained significantly reduced by 30 and 20%, respectively, in group 2, and recovered with AT within 60 min in group 3 to almost the same extent as in group 1. A massive increase in the tissue malondialdehyde concentration, indicative of lipid peroxidation, occurred in the beginning of reperfusion of warm-ischemically damaged donor livers, which in group 3 with AT tended to be less pronounced than in group 2 without AT. The GSSG/GSH ratio reflecting intracellular oxidant stress averaged 3.3 . 10(-3) in group 1 between 15 and 60 min reperfusion. In group 3 AT resulted in comparably low values averaging 3.8 . 10(-3), while in warm-ischemically damaged livers without AT of group 2 this ratio was significantly and continuously elevated averaging 5.8 . 10(-3). It is concluded from the different sequences of the various effects of allopurinol, that AT ameliorated the energy metabolism of warm-ischemically damaged livers probably due to the salvage of substrates, but that the reduction of oxidant stress provided by AT is not due to this improvement of energy metabolism but to a reduction in the xanthine oxidase-mediated production of free radicals.