GLUTATHIONE DEFICIENCY ACCENTUATES HEPATOCELLULAR FLUID ACCUMULATION AFTER ISCHEMIA-REPERFUSION

Liver ischemia-reperfusion is known to be associated with free radical -mediated hepatocellular damage but alterations in hepatocellular flui d flux under these conditions are incompletely understood. Deficiency of the antioxidant glutathione, which increases the liver's susceptibi lity to ischemia-reperfusion injury, may exacerbate pathological fluid shifts. This study examined alterations in hepatic fluid dynamics dur ing liver ischemia-reperfusion in glutathione-deficient and glutathion e-replete rats. Normal and glutathione-deficient rats underwent liver ischemia-reperfusion. Changes in hepatic extra- and intracellular flui d were monitored by calculating extra- and intracellular conductance f rom liver multifrequency bioelectrical impedance measurements. Liver m alonyl dialdehyde content and plasma transaminase concentrations were measured and correlated with changes in hepatic impedance. Hepatic ext racellular conductance decreased during ischemia and returned toward b aseline values during reperfusion in a similar fashion in both study g roups. Intracellular conductance increased during ischemia in both gro ups and continued to rise during the initial phase of reperfusion befo re falling toward normal. Glutathione-deficient rats had a significant ly higher intracellular conductance during early reperfusion compared to controls. Glutathione-depleted rats also had higher serum transamin ases and liver malonyl dialdehyde content following reperfusion. Intra cellular and extracellular conductance were significantly correlated w ith hepatic malonyl dialdehyde content. We conclude that (1) liver isc hemia-reperfusion results in movement of fluid from the extracellular to intracellular space with hepatocellular swelling; (2) glutathione d eficiency accentuates hepatocyte swelling following ischemia-reperfusi on; and (3) changes in extra- and intracellular fluid are related to t he severity of membrane damage. Multifrequency impedance analysis can be used to monitor real-time changes in hepatocyte injury and to study the effect of potential therapeutic interventions. (C) 1994 Academic Press, Inc.