Failure of Oxygen-free Radical Scavengers to Improve Postischemic Liver Function

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Abstract
Previous investigations have demonstrated reduction of postischemic organ injury with improved flow rates following administration of superoxide dismutase (SOD) and catalase (CAT) just before reperfusion. Presumably these oxygen-free radical scavengers provide protection against oxygen-free radicals produced during reoxygenation, but the site of action remains unclear. The present study was designed to determine the effect of SOD/CAT on hepatic function following global ischemia independent of flow. Livers obtained from Sprague-Dawley rats fasted 24 hours were perfused with Krebs-Henseleit buffer containing 5 mM lactate for 130 minutes. Following a 30-minute control period, livers were subjected to 55 minutes of warm, global ischemia. The control group (N =12) was reperfused under oxygenated conditions for an additional 45 minutes. Two other groups (TV=9; N=4) were reperfused under identical conditions with administration of 150,000 U/L or 450,000 U/L of SOD/CAT 3 minutes before reperfusion. Hepatic flow returned to normal levels following ischemia, but gluconeogenic activity and bile production remained significantly depressed. No significant recovery of gluconeogenic activity or bile production was noted when SOD/CAT was administered before reperfusion. These results demonstrate that in the absence of flow augmentation SOD/CAT do not provide protection from oxygen-free radicals following global ischemia in the isolated rat liver. This implies that previously reported reductions of postischemic reperfusion injury, where blood flow improved as well, may be due to oxygen-free radical scavenging within the vascular network resulting in enhanced organ perfusion and, therefore, improved organ function.