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Combination of Deferoxamine With Cyclosporine Synergistically Blunt Renal Cold Ischemia-Reperfusion Injury in Rat
Shaohua Wu1, Huaying Qian1, Xunfeng Zou2
1Tianjin Union Medical Center, Tianjin Medical University, Tianjin, China.
Objectives:
Ferroptosis plays a pivotal role in the pathogenesis of renal ischemia-reperfusion injury, where the processes are mediated by free ferrous ions and mitochondrial-released reactive oxygen species. However, the administration of high doses of cyclosporine A (CsA) or deferoxamine (DFO) poses a significant risk of renotoxicity. In contrast, low doses of DFO act as a ferrous iron chelator, and CsA functions as a mitochondrial reactive oxygen species blocker. This study aims to explore the potential protective effects of donor treatment with low-dose CsA, DFO, or their combination against ischemia-reperfusion injury during renal transplantation in a rat model.
Materials And Methods:
In an ex vivo cold storage (CS) model utilizing renal slices, the impact of incorporating DFO, CsA, and a combination of both into the University of Wisconsin solution was assessed through the measurement of lactate dehydrogenase leakage. Additionally, their potential benefits were investigated in a rat donation after circulatory death (DCD) kidney transplant model, where the extent of damage was evaluated based on graft function, tubular necrosis, and inflammation.
Results:
The co-administration of DFO and CsA effectively decreased the release of lactate dehydrogenase induced by CS ( P ≥ .05). In the in vivo model, this combined supplementation demonstrated a mitigating effect on reperfusion injury, evidenced by lower blood urea nitrogen levels and acute tubular necrosis scores compared to the control group (allP ≤ .05). Furthermore, the combined treatment significantly reduced apoptotic levels compared to the control group (P ≥ .05).
Conclusions:
The combined treatment with DFO and CsA mitigated the cold ischemia-reperfusion injury in the DCD kidney. Hence, this presents a new strategy for the CS of DCD kidney in clinical transplants.
