N-acetylcysteine protects from glutathione depletion in rats exposed to hyperoxia

Karen Shattuck, David K. Rassin, Chali D. Grinnell

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background: N-acetylcysteine (NAC) may protect against oxidative injury by providing cysteine for glutathione (GSH) biosynthesis or by direct reactions with electrophiles. We have recently shown that hyperoxic exposure of rats prior to liver perfusion is associated with significant decreases in hepatic GSH and significant changes in biliary amino acid concentrations. We hypothesized that NAC administration during hyperoxic exposure would prevent depletion of hepatic GSH by providing cysteine for GSH biosynthesis. Methods: NAC was administered during two conditions known to induce GSH depletion: hyperoxic exposure and biochemical inhibition of GSH synthesis using buthionine sulfoximine (BSO). After 48 hours, GSH concentrations in bile, liver and perfusate and biliary amino acid concentrations were determined using isolated perfused liver preparations. Results: Administration of NAC to rats maintained in normoxic or hyperoxic conditions, prior to liver perfusion, resulted in dose-dependent increases in GSH concentrations in bile, liver and perfusate, increases in bile flow rates and changes in biliary amino acid concentrations. When BSO was given concurrently with NAC in normal or hyperoxic conditions, these effects were not observed, and oxidant stress was evident. Conclusions: NAC prevents oxidant stress during hyperoxic exposure, most likely by supplying cysteine as a precursor for GSH synthesis.

Original languageEnglish (US)
Pages (from-to)228-233
Number of pages6
JournalJournal of Parenteral and Enteral Nutrition
Volume22
Issue number4
StatePublished - 1998

Fingerprint

hyperoxia
acetylcysteine
Hyperoxia
Acetylcysteine
Glutathione
glutathione
liver
Liver
rats
bile
Bile
Buthionine Sulfoximine
Cysteine
cysteine
Amino Acids
Oxidants
oxidants
amino acids
Perfusion
biosynthesis

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Food Science

Cite this

N-acetylcysteine protects from glutathione depletion in rats exposed to hyperoxia. / Shattuck, Karen; Rassin, David K.; Grinnell, Chali D.

In: Journal of Parenteral and Enteral Nutrition, Vol. 22, No. 4, 1998, p. 228-233.

Research output: Contribution to journalArticle

@article{5a4d1aa89eef4ab58c112c8b8dce7377,
title = "N-acetylcysteine protects from glutathione depletion in rats exposed to hyperoxia",
abstract = "Background: N-acetylcysteine (NAC) may protect against oxidative injury by providing cysteine for glutathione (GSH) biosynthesis or by direct reactions with electrophiles. We have recently shown that hyperoxic exposure of rats prior to liver perfusion is associated with significant decreases in hepatic GSH and significant changes in biliary amino acid concentrations. We hypothesized that NAC administration during hyperoxic exposure would prevent depletion of hepatic GSH by providing cysteine for GSH biosynthesis. Methods: NAC was administered during two conditions known to induce GSH depletion: hyperoxic exposure and biochemical inhibition of GSH synthesis using buthionine sulfoximine (BSO). After 48 hours, GSH concentrations in bile, liver and perfusate and biliary amino acid concentrations were determined using isolated perfused liver preparations. Results: Administration of NAC to rats maintained in normoxic or hyperoxic conditions, prior to liver perfusion, resulted in dose-dependent increases in GSH concentrations in bile, liver and perfusate, increases in bile flow rates and changes in biliary amino acid concentrations. When BSO was given concurrently with NAC in normal or hyperoxic conditions, these effects were not observed, and oxidant stress was evident. Conclusions: NAC prevents oxidant stress during hyperoxic exposure, most likely by supplying cysteine as a precursor for GSH synthesis.",
author = "Karen Shattuck and Rassin, {David K.} and Grinnell, {Chali D.}",
year = "1998",
language = "English (US)",
volume = "22",
pages = "228--233",
journal = "JPEN. Journal of parenteral and enteral nutrition",
issn = "0148-6071",
publisher = "SAGE Publications Inc.",
number = "4",

}

TY - JOUR

T1 - N-acetylcysteine protects from glutathione depletion in rats exposed to hyperoxia

AU - Shattuck, Karen

AU - Rassin, David K.

AU - Grinnell, Chali D.

PY - 1998

Y1 - 1998

N2 - Background: N-acetylcysteine (NAC) may protect against oxidative injury by providing cysteine for glutathione (GSH) biosynthesis or by direct reactions with electrophiles. We have recently shown that hyperoxic exposure of rats prior to liver perfusion is associated with significant decreases in hepatic GSH and significant changes in biliary amino acid concentrations. We hypothesized that NAC administration during hyperoxic exposure would prevent depletion of hepatic GSH by providing cysteine for GSH biosynthesis. Methods: NAC was administered during two conditions known to induce GSH depletion: hyperoxic exposure and biochemical inhibition of GSH synthesis using buthionine sulfoximine (BSO). After 48 hours, GSH concentrations in bile, liver and perfusate and biliary amino acid concentrations were determined using isolated perfused liver preparations. Results: Administration of NAC to rats maintained in normoxic or hyperoxic conditions, prior to liver perfusion, resulted in dose-dependent increases in GSH concentrations in bile, liver and perfusate, increases in bile flow rates and changes in biliary amino acid concentrations. When BSO was given concurrently with NAC in normal or hyperoxic conditions, these effects were not observed, and oxidant stress was evident. Conclusions: NAC prevents oxidant stress during hyperoxic exposure, most likely by supplying cysteine as a precursor for GSH synthesis.

AB - Background: N-acetylcysteine (NAC) may protect against oxidative injury by providing cysteine for glutathione (GSH) biosynthesis or by direct reactions with electrophiles. We have recently shown that hyperoxic exposure of rats prior to liver perfusion is associated with significant decreases in hepatic GSH and significant changes in biliary amino acid concentrations. We hypothesized that NAC administration during hyperoxic exposure would prevent depletion of hepatic GSH by providing cysteine for GSH biosynthesis. Methods: NAC was administered during two conditions known to induce GSH depletion: hyperoxic exposure and biochemical inhibition of GSH synthesis using buthionine sulfoximine (BSO). After 48 hours, GSH concentrations in bile, liver and perfusate and biliary amino acid concentrations were determined using isolated perfused liver preparations. Results: Administration of NAC to rats maintained in normoxic or hyperoxic conditions, prior to liver perfusion, resulted in dose-dependent increases in GSH concentrations in bile, liver and perfusate, increases in bile flow rates and changes in biliary amino acid concentrations. When BSO was given concurrently with NAC in normal or hyperoxic conditions, these effects were not observed, and oxidant stress was evident. Conclusions: NAC prevents oxidant stress during hyperoxic exposure, most likely by supplying cysteine as a precursor for GSH synthesis.

UR - http://www.scopus.com/inward/record.url?scp=0031780624&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031780624&partnerID=8YFLogxK

M3 - Article

VL - 22

SP - 228

EP - 233

JO - JPEN. Journal of parenteral and enteral nutrition

JF - JPEN. Journal of parenteral and enteral nutrition

SN - 0148-6071

IS - 4

ER -