Changes in glutathione concentration in hypothermically perfused dog kidneys.
A loss of glutathione from the kidney can cause increased sensitivity to oxygen free radical-induced injury. In this study we investigated the effects of kidney preservation on glutathione and how various glutathione precursors affect glutathione concentration in the dog kidney. During 5-day continuous machine perfusion of the kidney at 5 degrees C, a loss of glutathione from the cortex tissue was seen (24% +/- 1% glutathione remained after 5 days). Perfusion with reduced glutathione (GSH, 3 mmol/L) suppressed this loss (77% +/- 11% of glutathione remained after 5 days). Oxidized glutathione (GSSG) did not prevent the loss of glutathione. The addition of the three amino acids that make up glutathione (glycine, glutamic acid, and cysteine, 3 mmol/L each) also suppressed the loss of glutathione (82% +/- 13% remained at 5 days). The glutathione precursor, thioproline, a cysteine delivery compound, in combination with glycine and glutamic acid (3 mmol/L each), stimulated the synthesis of glutathione in the kidney during hypothermic perfusion (137% +/- 23% of control values at 5 days). The increase in tissue glutathione stimulated by GSH or other precursors was sensitive to the glutathione synthetase inhibitor, buthionine sulfoximine. This indicated the existence of active glutathione metabolism even at 5 degrees C in perfused kidneys. This study showed that in kidney preservation a loss of glutathione occurred that could be suppressed by the addition of various precursors for glutathione synthesis. The loss of glutathione from preserved kidneys may be one cause of posttransplant renal injury that could be prevented by use of the appropriate glutathione precursors.
Boudjema
K
K
Department of Surgery, University of Wisconsin, Madison.
Lindell
S L
SL
Southard
J H
JH
Belzer
F O
FO
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D019328:Buthionine Sulfoximine; D003080:Cold Temperature; D004228:Dithionitrobenzoic Acid / Q000494:pharmacology; D004285:Dogs; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism*; D019803:Glutathione Disulfide; D007668:Kidney / Q000378:metabolism*; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D009926:Organ Preservation / Q000379:methods*; D009994:Osmolar Concentration; D010477:Perfusion; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D013997:Time Factors; D014018:Tissue Distribution
D000963:Antimetabolites; D013438:Sulfhydryl Compounds; D013844:Thiazoles; D053778:Thiazolidines; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D004228:Dithionitrobenzoic Acid; C003438:thiazolidine-4-carboxylic acid; D005978:Glutathione; D019803:Glutathione Disulfide