Abstract
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 CCl4 (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 CCl4 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 CCl4, 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 CCl4 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.
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Abbreviations
- SAM:
-
S-adenosylmethionine
- MAT:
-
methionine adenosyltransferase
- SAH:
-
S-adenosylhomocys-teine
- CßS:
-
cystathionine ß-synthase
- CγL:
-
cystathionine γ-lyase
- GSH:
-
glutathione
- CDO:
-
cysteine dioxygenase
- GCL:
-
glutamate cysteine ligase
- AST:
-
aspartate aminotransferase
- ALT:
-
alanine aminotransferase
- sCr:
-
serum creatinine
- BUN:
-
blood urea nitrogen
- MDA:
-
malondialdehyde
- GGT:
-
γ-glutamyl-transferase
- ER:
-
endoplasmic reticulum
- LPS:
-
lipopolysaccharide
- ANIT:
-
a-naphthylisothiocyanate
- GSSG:
-
glutathione disulfide
- MRPs:
-
multidrug resistance proteins
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Kim, S.J., Kwon, D.Y., Choi, K.H. et al. Impaired Metabolomics of Sulfur-Containing Substances in Rats Acutely Treated with Carbon Tetrachloride. Toxicol Res. 24, 281–287 (2008). https://doi.org/10.5487/TR.2008.24.4.281
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DOI: https://doi.org/10.5487/TR.2008.24.4.281