Hyperoxia and glutathione depletion in the isolated perfused rat liver.
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 propargyglycine (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.


CONCLUSIONS
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.
Shattuck
K E
KE
Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555-0526, USA.
Grinnell
C D
CD
Keeney
S E
SE
Noworyta
K
K
Rassin
D K
DK
D000480:Alkynes / Q000494:pharmacology; D000603:Amino Acids, Sulfur / Q000032:analysis; D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism*; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D018496:Hyperoxia / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009924:Organ Culture Techniques; D010100:Oxygen / Q000008:administration & dosage; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley
D000480:Alkynes; D000603:Amino Acids, Sulfur; D004791:Enzyme Inhibitors; D019328:Buthionine Sulfoximine; C009055:propargylglycine; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D010100:Oxygen; D005998:Glycine