PREVENTION OF REOXYGENATION INJURY BY SODIUM-SALICYLATE IN ISOLATED-PERFUSED RAT-LIVER

Sodium salicylate can be used as a chemical trap for hydroxyl radicals , the most damaging reactive oxygen species. Because reactive oxygen s pecies are involved in the pathogenesis of hepatic hypoxia/reoxygenati on injury, the goal of this study was to determine if trapping hydroxy l radicals with salicylate would prevent or at least ameliorate such i njury. Isolated rat livers, continuously perfused with Krebs-Henseleit bicarbonate buffer in the presence or absence of salicylate (2 mM), w ere exposed, after 30 min of recovery, to 60 min of hypoxia, followed by 30 min of reoxygenation. During reoxygenation, control livers exper ienced a sharp increase in the rate of lactic dehydrogenase release, t aken as index of cell injury, protein carbonyl content, and malondiald ehyde, taken as index of protein oxidation and lipid peroxidation, res pectively. The presence of salicylate in the solution perfusion signif icantly reduced the rate of lactic dehydrogenase release, protein carb onyl content, and malondialdehyde production during reoxygenation. Hep atic histology documented a significantly reduced cell injury in salic ylate-perfused livers compared to control livers. These data suggest t hat the hydroxyl radical chemical trap sodium salicylate, acting as an antioxidant, may represents an effective agent to reduce liver injury due to hypoxia/reoxygenation in a model of isolated-perfused rat live r. (C) 1998 Elsevier Science Inc.