PYRUVATE REDUCES ANOXIC INJURY AND FREE-RADICAL FORMATION IN PERFUSEDRAT HEPATOCYTES

The effects of 5 mM pyruvate on anoxic injury, superoxide (O-2(-.)) an d hydrogen peroxide (H2O2) generation, and lactate dehydrogenase (LDH) release during reoxygenation after 2.5 h anoxia were studied in perfu sed rat hepatocytes. When pyruvate was present during anoxia and reoxy genation, there was little anoxic injury, and the generation of free r adicals and LDH release during reoxygenation were reduced 50-60%. When pyruvate was added during reoxygenation, there was no decrease in O-2 (-.) or LDH release, although H2O2 formation was depressed. Free radic al formation and anoxic/reperfusion injury were significantly reduced when pyruvate was added during the anoxic period only. Pyruvate reduce d the deleterious effects of 10 mu M antimycin A by preventing the inc rease in O-2(-.) formation and LDH release evoked by the inhibitor. Th ese results indicate that pyruvate protected hepatocytes against anoxi c injury and that its protective action occurred principally during an oxia and not during reoxygenation. Pyruvate appeared to act at a mitoc hondrial site, since it reduced the deleterious effects of antimycin A .