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Amelioration of galactosamine‐induced acute hepatic injury by betaine in rats
Author(s) -
Choi Yeo Jin,
Na Jong Deok,
Kim Young Chul
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb627
Subject(s) - betaine , methionine , putrescine , spermidine , liver injury , glutathione , ornithine , medicine , biochemistry , homocysteine , endocrinology , chemistry , transaminase , alanine transaminase , ornithine aminotransferase , arginine , biology , enzyme , amino acid
Galactosamine (GalN) is a potent hepatotoxicant that inhibits RNA and protein synthesis via depletion of uridine nucleotide in the liver. Earlier studies suggested that some endogenous sulfur‐containing substances, particularly glutathione (GSH) and/or S‐adenosylmethionine (SAM), might antagonize the induction of liver injury by GalN. In this study, we determined the effect of betaine, a methyl donor used for remethylation of homocysteine to methionine, against GalN‐induced acute liver injury in association with alterations in the metabolomics of sulfur‐containing amino acids and related substances in the liver. Male Sprague‐Dawley rats were supplemented with betaine (1 % in drinking water) for 2 weeks prior to a GalN challenge (400 mg/kg, ip). Rats were sacrificed 24 h later for the assay. GalN treatment elevated serum alanine transaminase (ALT), aspartate transaminase (AST), and sorbitol dehydrogenase (SDH) activities significantly, and these changes were prevented by betaine supplementation. Histopathological examination revealed 30 % of multifocal necrosis with macrophage infiltration throughout the liver of GalN‐treated rats, which was also inhibited by betaine supplementation. GalN treatment increased methionine, but not SAM levels in the liver. Betaine supplementation further increased the hepatic levels of methionine, SAM, and the activity of methionine adenosyltransferase (MAT), an enzyme mediating the biosynthesis of SAM from methionine. However, hepatic GSH contents were not affected by betaine or GalN. GalN treatment elevated ornithine and spermidine levels significantly, but decreased putrescine levels in the liver, suggesting that the metabolic conversion of putrescine from ornithine was impaired. Betaine supplementation increased hepatic putrescine and spermidine levels significantly, but ornithine levels were unaltered. It is suggested that the hepatoprotective effect of betaine against GalN‐induced liver injury may be associated with an enhancement of polyamine biosynthesis via induction of MAT activity and SAM availability in the liver. Support or Funding Information Supported by National Research Foundation (NRF) grants (No. 2014‐R1A2A1A11052967 and No. 2009‐0083533) funded by the Ministry of Education, Science and Technology (MEST), Korea.