Hyperoxia and glutathione depletion in the isolated perfused rat liver

Karen Shattuck, Chali D. Grinnell, Susan E. Keeney, Kelli Noworyta, David K. Rassin

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: Hepatic stores of glutathione may be depleted by hyperoxic exposure or poor nutritional status. We studied the effects of hyperoxia or hepatic glutathione depletion on bile flow rates, and on biliary concentrations of glutathione and amino acids. Methods: Glutathione depletion was induced in vivo by 1) hyperoxic exposure (O2) for 48 hours, 2) inhibition of glutathione synthesis by treatment with buthionine sulfoximine (BSO), 3) a combination of BSO + O2, or 4) inhibition of cysteine synthesis by propargylglycine (PPG). Livers were then isolated and perfused. Results: Glutathione concentrations in bile, liver, and perfusate were significantly decreased by all treatments. Bile flow was significantly decreased in groups treated with BSO or O2 + BSO, and perfusate LDH was increased by O2 + BSO or PPG. Significant changes in biliary amino acid concentrations included decreased sulfur-containing amino acids and increased branched-chain amino acids in groups treated with BSO, PPG, or O2; and increased essential amino acids in groups treated with O2 or PPG. Conclusion: Oxygen exposure or inhibition of glutathione synthesis results in significant decreases in hepatic, perfusate and biliary glutathione concentrations, and increases in biliary amino acids. A decrease in bile flow rate was associated only with the most severe glutathione depletion.

Original languageEnglish (US)
Pages (from-to)576-583
Number of pages8
JournalJournal of Investigative Medicine
Volume45
Issue number9
StatePublished - 1997

Fingerprint

Hyperoxia
Liver
Buthionine Sulfoximine
Glutathione
Rats
Bile
Amino Acids
Flow rate
Sulfur Amino Acids
Branched Chain Amino Acids
Essential Amino Acids
Nutritional Status
Sulfur
Cysteine
Oxygen
propargylglycine

Keywords

  • Amino acids
  • Antioxidant injury
  • Bile flow
  • Oxy-gen exposure

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Shattuck, K., Grinnell, C. D., Keeney, S. E., Noworyta, K., & Rassin, D. K. (1997). Hyperoxia and glutathione depletion in the isolated perfused rat liver. Journal of Investigative Medicine, 45(9), 576-583.

Hyperoxia and glutathione depletion in the isolated perfused rat liver. / Shattuck, Karen; Grinnell, Chali D.; Keeney, Susan E.; Noworyta, Kelli; Rassin, David K.

In: Journal of Investigative Medicine, Vol. 45, No. 9, 1997, p. 576-583.

Research output: Contribution to journalArticle

Shattuck, K, Grinnell, CD, Keeney, SE, Noworyta, K & Rassin, DK 1997, 'Hyperoxia and glutathione depletion in the isolated perfused rat liver', Journal of Investigative Medicine, vol. 45, no. 9, pp. 576-583.
Shattuck, Karen ; Grinnell, Chali D. ; Keeney, Susan E. ; Noworyta, Kelli ; Rassin, David K. / Hyperoxia and glutathione depletion in the isolated perfused rat liver. In: Journal of Investigative Medicine. 1997 ; Vol. 45, No. 9. pp. 576-583.
@article{ef87835b27f2457bb206d175825c3039,
title = "Hyperoxia and glutathione depletion in the isolated perfused rat liver",
abstract = "Background: Hepatic stores of glutathione may be depleted by hyperoxic exposure or poor nutritional status. We studied the effects of hyperoxia or hepatic glutathione depletion on bile flow rates, and on biliary concentrations of glutathione and amino acids. Methods: Glutathione depletion was induced in vivo by 1) hyperoxic exposure (O2) for 48 hours, 2) inhibition of glutathione synthesis by treatment with buthionine sulfoximine (BSO), 3) a combination of BSO + O2, or 4) inhibition of cysteine synthesis by propargylglycine (PPG). Livers were then isolated and perfused. Results: Glutathione concentrations in bile, liver, and perfusate were significantly decreased by all treatments. Bile flow was significantly decreased in groups treated with BSO or O2 + BSO, and perfusate LDH was increased by O2 + BSO or PPG. Significant changes in biliary amino acid concentrations included decreased sulfur-containing amino acids and increased branched-chain amino acids in groups treated with BSO, PPG, or O2; and increased essential amino acids in groups treated with O2 or PPG. Conclusion: Oxygen exposure or inhibition of glutathione synthesis results in significant decreases in hepatic, perfusate and biliary glutathione concentrations, and increases in biliary amino acids. A decrease in bile flow rate was associated only with the most severe glutathione depletion.",
keywords = "Amino acids, Antioxidant injury, Bile flow, Oxy-gen exposure",
author = "Karen Shattuck and Grinnell, {Chali D.} and Keeney, {Susan E.} and Kelli Noworyta and Rassin, {David K.}",
year = "1997",
language = "English (US)",
volume = "45",
pages = "576--583",
journal = "Journal of Investigative Medicine",
issn = "1081-5589",
publisher = "Lippincott Williams and Wilkins",
number = "9",

}

TY - JOUR

T1 - Hyperoxia and glutathione depletion in the isolated perfused rat liver

AU - Shattuck, Karen

AU - Grinnell, Chali D.

AU - Keeney, Susan E.

AU - Noworyta, Kelli

AU - Rassin, David K.

PY - 1997

Y1 - 1997

N2 - Background: Hepatic stores of glutathione may be depleted by hyperoxic exposure or poor nutritional status. We studied the effects of hyperoxia or hepatic glutathione depletion on bile flow rates, and on biliary concentrations of glutathione and amino acids. Methods: Glutathione depletion was induced in vivo by 1) hyperoxic exposure (O2) for 48 hours, 2) inhibition of glutathione synthesis by treatment with buthionine sulfoximine (BSO), 3) a combination of BSO + O2, or 4) inhibition of cysteine synthesis by propargylglycine (PPG). Livers were then isolated and perfused. Results: Glutathione concentrations in bile, liver, and perfusate were significantly decreased by all treatments. Bile flow was significantly decreased in groups treated with BSO or O2 + BSO, and perfusate LDH was increased by O2 + BSO or PPG. Significant changes in biliary amino acid concentrations included decreased sulfur-containing amino acids and increased branched-chain amino acids in groups treated with BSO, PPG, or O2; and increased essential amino acids in groups treated with O2 or PPG. Conclusion: Oxygen exposure or inhibition of glutathione synthesis results in significant decreases in hepatic, perfusate and biliary glutathione concentrations, and increases in biliary amino acids. A decrease in bile flow rate was associated only with the most severe glutathione depletion.

AB - Background: Hepatic stores of glutathione may be depleted by hyperoxic exposure or poor nutritional status. We studied the effects of hyperoxia or hepatic glutathione depletion on bile flow rates, and on biliary concentrations of glutathione and amino acids. Methods: Glutathione depletion was induced in vivo by 1) hyperoxic exposure (O2) for 48 hours, 2) inhibition of glutathione synthesis by treatment with buthionine sulfoximine (BSO), 3) a combination of BSO + O2, or 4) inhibition of cysteine synthesis by propargylglycine (PPG). Livers were then isolated and perfused. Results: Glutathione concentrations in bile, liver, and perfusate were significantly decreased by all treatments. Bile flow was significantly decreased in groups treated with BSO or O2 + BSO, and perfusate LDH was increased by O2 + BSO or PPG. Significant changes in biliary amino acid concentrations included decreased sulfur-containing amino acids and increased branched-chain amino acids in groups treated with BSO, PPG, or O2; and increased essential amino acids in groups treated with O2 or PPG. Conclusion: Oxygen exposure or inhibition of glutathione synthesis results in significant decreases in hepatic, perfusate and biliary glutathione concentrations, and increases in biliary amino acids. A decrease in bile flow rate was associated only with the most severe glutathione depletion.

KW - Amino acids

KW - Antioxidant injury

KW - Bile flow

KW - Oxy-gen exposure

UR - http://www.scopus.com/inward/record.url?scp=0031306704&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031306704&partnerID=8YFLogxK

M3 - Article

VL - 45

SP - 576

EP - 583

JO - Journal of Investigative Medicine

JF - Journal of Investigative Medicine

SN - 1081-5589

IS - 9

ER -