Related Experiment Video
Updated: Nov 6, 2025
Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration
Published on: June 7, 2014
Mitochondria-targeted antioxidant MitoQ ameliorates ischaemia-reperfusion injury in kidney transplantation models
M Hamed1,2,3, A Logan2, A V Gruszczyk1,2,3
1Department of Surgery, University of Cambridge, Cambridge, UK.
Background:
Ischaemia-reperfusion (IR) injury makes a major contribution to graft damage during kidney transplantation. Oxidative damage to mitochondria is an early event in IR injury. Therefore, the uptake, safety, and efficacy of the mitochondria-targeted antioxidant MitoQ were investigated in models of transplant IR injury.
Methods:
MitoQ uptake by warm and cooled pairs of pig and declined human kidneys was measured when preserved in cold static storage or by hypothermic machine perfusion. Pairs of pigs' kidneys were exposed to defined periods of warm and cold ischaemia, flushed and stored at 4°C with or without MitoQ (50 nmol/l to 250 µmol/l), followed by reperfusion with oxygenated autologous blood in an ex vivo normothermic perfusion (EVNP). Pairs of declined human kidneys were flushed and stored with or without MitoQ (5-100 µmol/l) at 4°C for 6 h and underwent EVNP with ABO group-matched blood.
Results:
Stable and concentration-dependent uptake of MitoQ was demonstrated for up to 24 h in pig and human kidneys. Total blood flow and urine output were significantly greater in pig kidneys treated with 50 µmol/l MitoQ compared with controls (P = 0.006 and P = 0.007 respectively). In proof-of-concept experiments, blood flow after 1 h of EVNP was significantly greater in human kidneys treated with 50 µmol/l MitoQ than in controls (P ≤ 0.001). Total urine output was numerically higher in the 50-µmol/l MitoQ group compared with the control, but the difference did not reach statistical significance (P = 0.054).
Conclusion:
Mitochondria-targeted antioxidant MitoQ can be administered to ischaemic kidneys simply and effectively during cold storage, and may improve outcomes after transplantation.
Insights
Mitochondria-targeted antioxidant MitoQ effectively protects kidneys from ischaemia-reperfusion injury during transplantation. Administration during cold storage improved graft function in pig and human kidney models, suggesting enhanced transplant outcomes.
Area of Science:
- Nephrology
- Transplantation immunology
- Mitochondrial medicine
Background:
- Ischaemia-reperfusion (IR) injury significantly damages kidney grafts during transplantation.
- Mitochondrial oxidative damage is an early critical event in IR injury.
Purpose of the Study:
- To investigate the uptake, safety, and efficacy of MitoQ, a mitochondria-targeted antioxidant, in preclinical models of kidney transplant IR injury.
Main Methods:
- MitoQ uptake was measured in pig and human kidneys during cold static storage and hypothermic machine perfusion.
- Kidney pairs underwent defined IR injury, cold storage with or without MitoQ, followed by ex vivo normothermic perfusion (EVNP).
Main Results:
- MitoQ demonstrated stable, concentration-dependent uptake in both pig and human kidneys for up to 24 hours.
- Pig kidneys treated with 50 µmol/l MitoQ showed significantly improved blood flow and urine output post-IR.
- Human kidneys treated with 50 µmol/l MitoQ exhibited significantly greater blood flow during EVNP.
Conclusions:
- MitoQ can be effectively administered to kidneys during cold storage to mitigate IR injury.
- MitoQ holds promise for improving graft function and outcomes in kidney transplantation.
