The effect of high-dose
alanine on survival and liver function in rats with
acute liver failure caused by a lethal dose of D-
galactosamine (D-gal) was studied. Greater than 90% of control animals died within 5 days after D-gal injection, but
alanine significantly decreased mortality, even when treatment was started at 12 hours after D-gal injection.
Alanyl-glutamine had a slight effect, but
glucose produced no improvement. There was marked elevation of the plasma
aspartate transaminase (AST) level, prolongation of the prothrombin time, and a decrease of the arterial
ketone body ratio (AKBR) and hepatic
adenosine triphosphate (
ATP) content within 12 hours after D-gal injection. The AKBR decreased in parallel with the decrease of the hepatic
ATP content. These parameters were significantly improved in
alanine-treated rats at 48 hours after the induction of liver damage, which was just before control rats began to die. The hepatic
ATP content was significantly greater in
alanine-treated rats than in the other rats (including normal controls), but
glucose pretreatment had no effect. It was also found that the liver labeling index of partially hepatectomized rats was significantly elevated by
alanine administration at 3 hours before measurement. In conclusion,
alanine is effective for the treatment of experimental
acute liver failure, probably caused by promotion of
ATP synthesis. Ala may be a good candidate for clinical application because of its preventive effect on hepatocyte
necrosis and its promotive effect on liver regeneration.