Impaired metabolomics of sulfur-containing substances in rats acutely treated with carbon tetrachloride

Sun Ju Kim, Do Young Kwon, Kwon Hee Choi, DalWoong Choi, Young Chul Kim

Research output: Contribution to journalArticle

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 4̃8 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 sulfurcontaining amino acids and related substances. The major metabolites and products of the transsulfuration 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.

Original languageEnglish
Pages (from-to)281-287
Number of pages7
JournalToxicological Research
Volume24
Issue number4
DOIs
Publication statusPublished - 2008 Dec 1

Fingerprint

Metabolomics
Carbon Tetrachloride
Sulfur
Liver
Rats
Plasmas
Methionine
Cysteine
Cysteine Dioxygenase
Methionine Adenosyltransferase
Glutamate-Cysteine Ligase
Amino Acids
S-Adenosylmethionine
Wounds and Injuries
Poisons
Metabolites
Metabolism
Sulfur Amino Acids
Glutathione
Kidney

Keywords

  • Carbon tetrachloride
  • Glutathione
  • S-adenosylmethionine
  • Taurine
  • Transsulfuration

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Impaired metabolomics of sulfur-containing substances in rats acutely treated with carbon tetrachloride. / Kim, Sun Ju; Kwon, Do Young; Choi, Kwon Hee; Choi, DalWoong; Kim, Young Chul.

In: Toxicological Research, Vol. 24, No. 4, 01.12.2008, p. 281-287.

Research output: Contribution to journalArticle

Kim, Sun Ju ; Kwon, Do Young ; Choi, Kwon Hee ; Choi, DalWoong ; Kim, Young Chul. / Impaired metabolomics of sulfur-containing substances in rats acutely treated with carbon tetrachloride. In: Toxicological Research. 2008 ; Vol. 24, No. 4. pp. 281-287.
@article{b3f0bb2f5a0c42f1aa8d6a7c60da93a6,
title = "Impaired metabolomics of sulfur-containing substances in rats acutely treated with carbon tetrachloride",
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 4̃8 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 sulfurcontaining amino acids and related substances. The major metabolites and products of the transsulfuration 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.",
keywords = "Carbon tetrachloride, Glutathione, S-adenosylmethionine, Taurine, Transsulfuration",
author = "Kim, {Sun Ju} and Kwon, {Do Young} and Choi, {Kwon Hee} and DalWoong Choi and Kim, {Young Chul}",
year = "2008",
month = "12",
day = "1",
doi = "10.5487/TR.2008.24.4.281",
language = "English",
volume = "24",
pages = "281--287",
journal = "Toxicological Research",
issn = "1976-8257",
publisher = "Koreal Association of Medical Journal Editors",
number = "4",

}

TY - JOUR

T1 - Impaired metabolomics of sulfur-containing substances in rats acutely treated with carbon tetrachloride

AU - Kim, Sun Ju

AU - Kwon, Do Young

AU - Choi, Kwon Hee

AU - Choi, DalWoong

AU - Kim, Young Chul

PY - 2008/12/1

Y1 - 2008/12/1

N2 - 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 4̃8 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 sulfurcontaining amino acids and related substances. The major metabolites and products of the transsulfuration 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.

AB - 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 4̃8 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 sulfurcontaining amino acids and related substances. The major metabolites and products of the transsulfuration 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.

KW - Carbon tetrachloride

KW - Glutathione

KW - S-adenosylmethionine

KW - Taurine

KW - Transsulfuration

UR - http://www.scopus.com/inward/record.url?scp=84880643067&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84880643067&partnerID=8YFLogxK

U2 - 10.5487/TR.2008.24.4.281

DO - 10.5487/TR.2008.24.4.281

M3 - Article

AN - SCOPUS:84880643067

VL - 24

SP - 281

EP - 287

JO - Toxicological Research

JF - Toxicological Research

SN - 1976-8257

IS - 4

ER -