EFFECT OF DIETHYLMALEATE ON LIVER EXTRACELLULAR GLUTATHIONE LEVELS BEFORE AND AFTER GLOBAL LIVER ISCHEMIA IN ANESTHETIZED RATS

Glutathione (GSH), present in a high concentration in the liver, serve s important protective functions. We investigated the effect of lowere d tissue GSH content, accomplished. by diethylmaleate (DEM) administra tion, on liver extracellular GSH levels before and after global ischem ia in anesthetized rats. Liver extracellular GSH levels were determine d hy microdialysis perfusion and an on-line high performance liquid ch romatography system. Global liver ischemia was induced by ligation of the hepatic pedicles including the hepatic artery, portal vein, and bi le duct. DEM (4 mmol/kg) significantly lowered both the liver tissue G SH levels (1.36 +/- 0.26 mu mol/g wet wt vs 9.50 +/- 0.55 mu mol/g wet wt for the untreated) and the liver extracellular GSH levels (4.3 +/- 2.4 mu M vs 25.2 +/- 8.7 mu M for the untreated). Global liver ischem ia induced a dramatic increase in the liver extracellular GSH level. A lthough the liver tissue GSH level was lowered following DEM treatment , DEM administration did not affect significantly ischemia-induced ele vation of extracellular GSH (when presented as fold increase relative to basal value). In conclusion, DEM showed a direct effect on liver ex tracellular GSH content in anesthetized rats. However, DEM treatment d id not affect the relative release of GSH following global liver ische mia. Copyright (C) 1997 Elsevier Science Inc.