Glycine has been shown to protect renal tubule cells and hepatocytes from
ischemia,
ATP depletion, and cold storage injury.
Glycine may be a useful additive to
organ preservation solutions or suppress
reperfusion injury by infusion into recipients of
liver transplantation. In this study, the effects of
glycine on survival and postoperative liver injury were studied in the rat and dog orthotopic transplant model. Rat livers preserved for 30 hr in the University of Wisconsin (
UW) solution were 50% viable (3 of 6 survivors for 7 days). When
glutathione was replaced by 10 mM
glycine, survival increased to 100% (6 of 6). There was a significant reduction in hepatocellular injury at the end of preservation (
lactate dehydrogenase [LDH] in the pretransplant flush-out of the liver was lower in the
glycine group) and after
transplantation (serum LDH concentration 6 hr after transplant was lower in the
glycine group). In the dog, omission of
glutathione from the
UW solution resulted in 33% survival (48-hr preservation model) versus 100% survival with
glutathione. Replacing
glutathione in the
UW solution by
glycine did not improve survival (33% after 48 hr of preservation). However, when
glycine was given to recipients of livers preserved in the
UW solution for 24 or 48 hr, there was a decrease in the degree of hepatocellular injury. After 48 hr of preservation, peak
aspartate aminotransferase,
alanine aminotransferase, and LDH were reduced by about 45-55% when
glycine was given to the recipient. Although the differences, with and without
glycine treatment of the recipients, did not reach statistical significance, there was a noticeable reduction in hepatocellular injury with
glycine. There was 100% survival of dogs in the groups that received livers preserved with the
UW solution plus or minus
glycine infusion. Hepatamine, a
parenteral nutrition solution containing
glycine and other
amino acids increased hepatocellular injury (higher concentrations of
aspartate aminotransferase,
alanine transferase, and LDH versus control 48-hr preserved livers), although all dogs survived. This study shows that
glycine is cytoprotective when administered to recipients of livers preserved for 24 or 48 hr and suppresses hepatocellular injury, as reflected in a reduction in the concentration of serum
enzymes. However, the differences, with and without
glycine, were, at best, marginal and further studies are needed to determine whether
glycine would make a significant improvement in liver preservation and prevent primary nonfunction.