Cytoprotective effect of glycine in cold stored canine renal tubules

Abstract

Reperfusion injury has been suggested to cause delayed graft function in renal transplantation. Methods to reduce reperfusion injury could lead to improved clinical renal transplantation. Glycine has been shown to suppress reperfusion injury in rabbit renal tubules and rat hepatocytes. In this study we have determined the effects of glycine on viability of isolated canine renal tubules. Renal tubules were cold stored at 4 degrees C under hypoxic conditions for up to 96 h in the UW solution and rewarmed to 37 degrees C for up to 2 h under oxygenated conditions to simulate reperfusion of an organ after cold static storage. Short-term storage (24 to 48 h) did not cause membrane injury (leakage of lactate dehydrogenase (LDH)) on rewarming. However, after 72 and 96 h cold storage reperfusion injury was evident and LDH leakage increased from about 25% to 59 +/- 3% and 71 +/- 2% at 72 and 96 h cold storage, respectively. The presence of 3 mM glycine in the reperfusion medium suppressed injury to cold-stored renal tubules. After cold storage for 72 and 96 h LDH leakage was reduced to control concentrations (31 +/- 3% and 29 +/- 1%, respectively). After cold storage for 72 h there was a reduction in ATP concentration in rewarmed renal tubules (3 nmol/mg protein at 48 h to 1.25 nmol/mg protein at 72 h). Also, there was a loss of mitochondrial functions including decreased stimulation of oxygen consumption by uncoupling of oxidative phosphorylation. Although glycine suppressed LDH leakage in renal tubules cold stored for 72 h it had no effect on the regeneration of ATP or mitochondrial functions, which remained depressed.(ABSTRACT TRUNCATED AT 250 WORDS)