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Changes in glutathione concentration in hypothermically perfused dog kidneys
K Boudjema1, S L Lindell, J H Southard
1Department of Surgery, University of Wisconsin, Madison.
The Journal of Laboratory and Clinical Medicine
|February 1, 1991
Summary
Kidney preservation causes glutathione loss, increasing injury risk. Supplementing with glutathione or its precursors during perfusion prevents this loss, potentially reducing post-transplant renal injury.
Area of Science:
- Nephrology
- Biochemistry
- Transplantation
Background:
- Glutathione depletion in kidneys elevates sensitivity to oxidative stress.
- Kidney preservation can lead to significant glutathione loss from renal cortex tissue.
Purpose of the Study:
- To investigate the impact of kidney preservation on glutathione levels.
- To evaluate the efficacy of various glutathione precursors in maintaining renal glutathione concentration during hypothermic perfusion.
Main Methods:
- Continuous machine perfusion of dog kidneys at 5°C for 5 days.
- Supplementation with reduced glutathione (GSH), oxidized glutathione (GSSG), or glutathione precursors (amino acids, thioproline).
- Assessment of glutathione concentration and metabolism using a glutathione synthetase inhibitor.
Main Results:
- A 76% loss of glutathione occurred in preserved kidneys over 5 days.
- Perfusion with GSH or a mixture of glycine, glutamic acid, and cysteine significantly suppressed glutathione loss.
- Thioproline, glycine, and glutamic acid stimulated glutathione synthesis, increasing levels beyond initial values.
- Active glutathione metabolism was evident even at 5°C, as indicated by sensitivity to buthionine sulfoximine.
Conclusions:
- Kidney preservation leads to glutathione depletion, a potential contributor to post-transplant renal injury.
- Supplementation with GSH or specific precursors can mitigate glutathione loss during kidney preservation.
- Targeted precursor administration may offer a strategy to prevent renal injury following transplantation.