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A loss of glutathione (GT) from the kidney can cause increased sensitivity to oxygen free radical-induced injury. In this study we investigated the effects of kidney preservation on GT concentration in the cortex tissue, and how various GT precursors affect GT concentration in the dog kidney. During five day continuous machine perfusion of the kidney at 5 degrees C, there was a loss of GT from the cortex tissue (524 +/- 1% GT remained after 5 days). Perfusion with reduced glutathione (GSH, 3 mM) suppressed this loss (77 +/- 11% of GT remained after 5 days). Oxidized glutathione (GSSG) did not prevent the loss of GT. The addition of the three amino acids that make up GT (glycine, glutamic acid, and cysteine, 3 mM each) stimulated the synthesis of GT in the kidney during hypothermic perfusion (137 +/- 23% of control values at 5 days). The increase in tissue GT stimulated by GSH or other precursors was sensitive to the GT synthetase inhibitor, buthionine sulfoximine. This indicated active GT metabolism even at 5 degrees C in perfused kidneys. This study showed that in kidney preservation there was a loss of GT that could be suppressed by the addition of various precursors for GT synthesis. The loss of GT from preserved kidneys may be one cause of post-transplant renal injury which could be prevented by utilization of the appropriate GT precursors.

In this study we have investigated the effects of hepatocytes glycogen storage on the quality of livers for transplantation. Rats were fed or fasted for 24 h and hepatocytes isolated and cold stored in UW solution for 24 and 48 hours. Viability of the cells was analyzed by LDH release after 2 hours incubation in L15 with O2. Also, rabbits were fed, fasted (48 h) or glucose fed (48 h) and livers cold stored for 6, 24 and 48 h in UW solution. Functions of the livers were analyzed by isolated perfusion for 2 hours. Hepatocytes from fasted rats released significantly more LDH than hepatocytes from fed rats after 24 and 48 h cold storage. In rabbit livers, fasting depleted glycogen by 85% but had no effect on ATP or glutathione concentration. Livers from fasted rabbits produced similar amount of bile, released similar concentrations of lactate dehydrogenase and aspartate transaminase into the perfusate, maintained similar concentrations of glutathione after 24 hours preservation when compared to fed animals. After 48 h preservation livers from fasted animals were less viable than livers from fed animals and the decrease of liver functions in livers from fasted animals preserved for 48 hours was prevented by feeding glucose. This study shows that liver glycogen storage in hepatocyte is an important metabolite for successful liver preservation. Glycogen may be a source for ATP and antioxydant synthesis during the early period of reperfusion.