Protection from hypoxic injury in cultured hepatocytes by glycine, alanine, and serine

Isolated hepatocytes from rat liver in primary culture rapidly lost viability under hypoxic conditions. In the presence of glycine, L-alanine or L-serine loss of viability under hypoxic conditions was greatly retarded. Glycine and L-serine already showed significant protection from hypoxic injury at a concentration of 0.1 mM; at 10 mM, all three amino acids offered almost complete protection. Beside these standard amino acids, 1-aminocyclopropane-1-carboxylic acid (ACPC) and sarcosine significantly decreased hypoxic injury of the hepatocytes, although to a lesser extent. Other amino acids tested provided only slight protection or had no effect on hypoxic injury of the hepatocytes. In the presence of the protective amino acids neither the ATP content nor the lactate production of the hypoxic hepatocytes were significantly affected. The addition of glycine, L-alanine and L-serine led to marked membrane alterations (blebs). These alterations, however, occurred without loss of viability and were reversible upon reoxygenation after up to 4 h of hypoxia.