N-acetylcysteine protects from glutathione depletion in rats exposed to hyperoxia.
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.
Shattuck
K E
KE
Department of Pediatrics, University of Texas Medical Branch, Galveston 77555-0526, USA.
Rassin
D K
DK
Grinnell
C D
CD
D000111:Acetylcysteine / Q000008:administration & dosage / Q000627:therapeutic use*; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001646:Bile / Q000378:metabolism; D005978:Glutathione / Q000172:deficiency* / Q000378:metabolism; D018496:Hyperoxia / Q000150:complications*; D008099:Liver / Q000378:metabolism; D008297:Male; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000596:Amino Acids; D011506:Proteins; D017392:Thiobarbituric Acid Reactive Substances; D005978:Glutathione; D000111:Acetylcysteine