Protection by glycine against chemical ischemia produced by cyanide in cultured hepatocytes.

The killing of cultured hepatocytes by cyanide accelerated phospholipid metabolism, with a reduction in cytoplasmic pH, but did not accelerate proteolysis. Alkalinization of the cytoplasm by monensin, a protonsodium exchange ionophore, enhanced the loss of viability and acceleration of phospholipid metabolism caused by cyanide. Thus, acidification of the cytoplasm appears to protect against the toxic effects of cyanide. Glycine reduced the killing of hepatocytes, concomitant with reduced phospholipid metabolism. The protective effect of glycine neither enhanced the reduction in cytoplasmic pH nor prevented the depletion of adenosine triphosphate (ATP) by cyanide. The mechanism of the protection exerted by glycine against chemical ischemia can be attributed neither to changes in cytoplasmic pH nor to the prevention of ATP depletion, but appears to be due to other mechanisms that have yet to be identified.