Cytoprotection by glycine against hypoxia-induced injury in cultured hepatocytes.

The aim of this study was to investigate the mechanism of cytoprotection by glycine against hypoxia-induced hepatocellular injury. Incubation under hypoxic conditions (95% N2 and 5% CO2) for 5 h induced about 50% cell death, but administration of glycine remarkably reduced hepatocellular death without preventing a loss in ATP content. Anaerobic glycolysis generated lactic acid, reducing extracellular pH, but glycine had no effect on changes in extracellular pH. Chloride-channel inhibitors [anthracene-9-carboxylic acid (A9C), furosemide, and strychnine] also significantly reduced hepatocellular death induced by hypoxia. These results suggest that the mechanism of protection by glycine against hypoxic injury is not related to the prevention of ATP depletion or to changes in extracellular pH, but may be due to inhibition of chloride ion influx into the hepatocyte.