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Mitoquinone Alleviates Donation after Cardiac Death Kidney Injury during Hypothermic Machine Perfusion in Rat Model
Anna Radajewska1, Jakub Szyller1, Anna Krzywonos-Zawadzka1
1Division of Clinical Chemistry and Laboratory Hematology, Department of Medical Laboratory Diagnostics, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland.
International Journal of Molecular Sciences
|October 14, 2023
Summary
Mitoquinone (MitoQ) protects kidneys from damage during preservation for transplantation. This mitochondria-targeted antioxidant reduces injury markers and apoptosis in machine-perfused donation after cardiac arrest (DCD) grafts.
Area of Science:
- Transplantation immunology
- Regenerative medicine
- Organ preservation
Background:
- Transplanted organs face damage from ischemia-reperfusion injury (IRI), especially kidneys from donation after cardiac arrest (DCD).
- Hypothermic machine perfusion (HMP) offers improved organ storage and a platform for graft treatment.
- Antioxidants, like Mitoquinone (MitoQ), are investigated for their potential to mitigate IRI by scavenging reactive oxygen species (ROS).
Purpose of the Study:
- To evaluate the protective effects of MitoQ administered during HMP on kidney grafts.
- To assess MitoQ's impact on IRI markers, oxidative stress, and apoptosis in DCD and donation after brainstem death (DBD) rat kidney models.
Main Methods:
- Rat kidneys from DBD and DCD donors were subjected to 22-hour HMP.
- MitoQ was added to the perfusate of DCD kidneys.
- Kidney injury marker (KIM-1), oxidative stress markers (ROS/RNS), apoptosis markers (caspase 3 and 9), and Akt signaling pathway were analyzed.
Main Results:
- MitoQ treatment significantly reduced KIM-1 levels, total ROS/RNS, and caspase activation.
- A decrease in phosphorylated Akt (pAkt) and the pAkt/total Akt ratio was observed in the MitoQ group.
- Warm ischemia time was confirmed as a negative factor, but MitoQ mitigated associated kidney injury.
Conclusions:
- MitoQ administered during HMP effectively reduces IRI in DCD kidney grafts.
- MitoQ inhibits apoptosis and decreases oxidative stress, offering a potential preconditioning strategy for DCD grafts.
- MitoQ shows promise as a therapeutic agent to improve the viability of DCD kidney grafts prior to transplantation.
