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Ebselen. Antioxidant capacity in renal preservation
J D Gower1, N J Lane, J G Goddard
1Section of Surgical Research, MRC Clinical Research Centre, Harrow, Middlesex, U.K.
Ebselen effectively reduced oxidative damage and edema in cold-preserved rabbit kidneys. However, it did not improve long-term kidney transplant survival in rabbits.
Area of Science:
- Biochemistry
- Nephrology
- Pharmacology
Background:
- Cold ischemia induces oxidative damage and edema in kidneys, impacting transplant outcomes.
- Ebselen is a potent antioxidant, but its metabolites' activities and its efficacy in organ preservation require investigation.
Purpose of the Study:
- To evaluate ebselen's ability to inhibit oxidative membrane damage in cold-ischemic rabbit kidneys.
- To assess the impact of ebselen on kidney edema and post-transplant outcomes.
Main Methods:
- In vitro assessment of ebselen and its metabolites' antioxidant capacity using a lipid peroxidation system.
- Preservation of rabbit kidneys under cold ischemia (72 hours) with or without ebselen.
- Measurement of lipid peroxidation markers (Schiff's bases, TBA-reactive material) and edema.
- Evaluation of long-term survival and function after kidney autotransplantation.
Main Results:
- Ebselen demonstrated potent antioxidant activity, significantly reducing oxidative markers and edema in preserved kidneys.
- Metabolite I showed no antioxidant activity, while Metabolite II was significantly less potent than ebselen.
- Despite reducing oxidative damage and edema, ebselen administration did not improve long-term survival or physiological/histological outcomes post-transplantation.
Conclusions:
- Ebselen protects kidneys against cold ischemia-induced oxidative damage and edema.
- Ebselen's therapeutic benefit in kidney transplantation is limited, as it does not enhance long-term graft survival.
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