Glycine prevention of cold ischemic injury in isolated hepatocytes.
Isolated hepatocytes suspended in a liver preservation solution (University of Wisconsin (UW) solution) and exposed to cold (5 degrees C) ischemia lose viability (LDH release) after 3 (76.5 +/- 2.6% extracellular LDH) and 4 days (90.3 +/- 5.7% extracellular LDH) storage when rewarmed (37 degrees C) in Krebs-Henseleit buffer. However, if 3 mM glycine is added to Krebs-Henseleit buffer the loss of LDH on rewarming was suppressed (% LDH = 24.4 +/- 2.2% and 33.2 +/- 3.0%, at 3 and 4 days, respectively). The protection by glycine could also be obtained by storing the hepatocytes in the UW solution containing 15 mM glycine and rewarming in the absence of glycine in Krebs-Henseleit buffer. There did not appear to be a relationship between the protection by glycine and glutathione concentration of the hepatocytes as shown by the lack of effect of a glutathione synthetase inhibitor (butathionine sulfoximine) on the protective effects of glycine. Other amino acids did not provide protection to hepatocytes exposed to cold ischemia. The mechanism of action of glycine is not known, but this compound may be important in improving cold storage of livers for transplantation.
Marsh
D C
DC
Department of Surgery, University of Wisconsin, Madison 53792.
Hjelmhaug
J A
JA
Vreugdenhil
P K
PK
Belzer
F O
FO
Southard
J H
JH
D000818:Animals; D002470:Cell Survival; D003080:Cold Temperature; D003451:Cryoprotective Agents; D005978:Glutathione / Q000378:metabolism; D005998:Glycine; D066298:In Vitro Techniques; D007511:Ischemia; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000098:blood supply / Q000166:cytology / Q000378:metabolism; D009926:Organ Preservation; D051381:Rats; D011919:Rats, Inbred Strains
D003451:Cryoprotective Agents; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D005998:Glycine