Mechanisms of the protective effect of L-alanine to D-galactosamine-induced hepatocellular injury: comparative studies of L-alanine and pyruvate.
The addition of L-alanine reduced lactate dehydrogenase leakage from primary cultured rat hepatocytes treated with galactosamine (D-gal), while D-alanine and other amino acids did not. However, the mechanisms have not yet been entirely clarified. In this study, we used various inhibitors of metabolism, i.e., aminooxyacetate, oligomycin, and quinolinic acid, to examine the relation between this protective effect and the metabolism of L-alanine. Quinolinic acid (10 mM) did not affect the hepatoprotective effect of L-alanine, while oligomycin (0.1 mug/ml) and aminooxyacetate (1 mM) eliminated the hepatoprotective effect of L-alanine. L-Alanine also increased the albumin secretion by cultured hepatocytes treated with D-gal, while pyruvate had little effect. It was revealed that the intracellular content of pyruvate did not increase as a result of addition of L-alanine. These results are consistent with the hypothesis that L-alanine metabolism is important for hepatoprotection, but pyruvate cannot be used as a substitute for L-alanine.
Ishizaki-Koizumi
Sonoko
S
Pharmaceutical Research Laboratories, Ajinomoto Co., Inc., 1-1, Suzuki-cho, Kawasaki-ku, Kawasaki 210-8681, Japan. sonoko-ishizaki@ajinomoto.com
Sonaka
Ichiro
I
Fujitani
Shoji
S
Nishiguchi
Shuhei
S
D000409:Alanine / Q000378:metabolism / Q000494:pharmacology*; D000418:Albumins / Q000378:metabolism; D000621:Aminoisobutyric Acids / Q000494:pharmacology; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D005688:Galactosamine / Q000037:antagonists & inhibitors*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D017093:Liver Failure / Q000378:metabolism / Q000517:prevention & control; D008297:Male; D009840:Oligomycins / Q000494:pharmacology; D019289:Pyruvic Acid / Q000494:pharmacology*; D017378:Quinolinic Acid / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000418:Albumins; D000621:Aminoisobutyric Acids; D009840:Oligomycins; D000625:Aminooxyacetic Acid; C100049:2-aminoisobutyric acid; D005688:Galactosamine; D019289:Pyruvic Acid; D007770:L-Lactate Dehydrogenase; D017378:Quinolinic Acid; D000409:Alanine