Effect of alanine on D-galactosamine-induced acute liver failure in rats.
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.
Life Science Laboratory, Central Research Laboratories, Ajinomoto Co., Inc., Yokohama, Japan.
K
K
Maezono
K
K
Mawatari
K
K
Kajiwara
A
A
Shinkai
T
T
Maki
D000255:Adenosine Triphosphate / Q000378:metabolism; D000409:Alanine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D004247:DNA / Q000096:biosynthesis; D005688:Galactosamine; D007657:Ketone Bodies / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000503:physiopathology; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley
D007657:Ketone Bodies; D005688:Galactosamine; D000255:Adenosine Triphosphate; D004247:DNA; D000409:Alanine