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Impaired Metabolomics of Sulfur-Containing Substances in Rats Acutely Treated with Carbon Tetrachloride

Impairment of hepatic metabolism of sulfur-containing amino acids has been known to be linked with induction of liver injury. We determined the early changes in the transsulfuration reactions in liver of rats challenged with a toxic dose of CCl(4) (2 mmol/kg, ip). Both hepatic methionine concentrati...

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Detalles Bibliográficos
Autores principales: Kim, Sun Ju, Kwon, Do Young, Choi, Kwon Hee, Choi, Dal Woong, Kim, Young Chul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Singapore 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7006244/
https://www.ncbi.nlm.nih.gov/pubmed/32038806
http://dx.doi.org/10.5487/TR.2008.24.4.281
Descripción
Sumario:Impairment of hepatic metabolism of sulfur-containing amino acids has been known to be linked with induction of liver injury. We determined the early changes in the transsulfuration reactions in liver of rats challenged with a toxic dose of CCl(4) (2 mmol/kg, ip). Both hepatic methionine concentration and methionine adenosyltransferase activity were increased, but S-adenosylmethionine level did not change. Hepatic cysteine was increased significantly from 4 h after CCl(4) treatment. Glutathione (GSH) concentration in liver was elevated in 4~8 h and then returned to normal in accordance with the changes in glutamate cysteine ligase activity. Cysteine dioxygenase activity and hypotaurine concentration were also elevated from 4 h after the treatment. However, plasma GSH concentration was increased progressively, reaching a level at least several fold greater than normal in 24 h. γ-Glutamyltransferase activity in kidney or liver was not altered by CCl(4), suggesting that the increase in plasma GSH could not be attributed to a failure of GSH cycling. The results indicate that acute liver injury induced by CCl(4) is accompanied with extensive alterations in the metabolomics of sulfur-containing amino acids and related substances. The major metabolites and products of the transsul-furation pathway, including methionine, cysteine, hypotaurine, and GSH, are all increased in liver and plasma. The physiological significance of the change in the metabolomics of sulfur-containing substances and its role in the induction of liver injury need to be explored in future studies.