Introduction: Ischemia-reperfusion injury (IRI) is a commonly encountered problem in organ transplantation. IRI is associated with delayed graft function and acute rejection; therefore IRI adversely affects the long-term survival of the graft. Ceria nanoparticles possess catalytic properties due to their ability to convert O^.₂^– to O₂, to generate Ce³⁺ from Ce⁴⁺, and then auto-regenerate Ce⁴⁺ from the reduction of Ce³⁺ or by reaction with HO^.. Ceria were also found to catalyze the degradation of H₂O₂, which depicts a multi-faceted mechanism to its antioxidant properties. In this study, we investigated protective effect of ceria-nanoparticle on IRI using a rat kidney IRI model.

Methods: Male, wild-type Lewis rats aged 3 months were utilized for this study. Unilateral renal IRI was accomplished using microvascular clamping of the left renal vascular bundle through a longitudinal skin incision of the abdomen. At the end of 45 minute of kidney warm ischemia, the clamp was removed and different doses of ceria-nanoparticles and PBS was injected intraperitoneally. At the end of the reperfusion period (24h), rats were sacrificed and kidney tissue was collected. Minced kidney tissue was used for Western-blot. Data from ceria-nanoparticles injection group were compared with IRI alone, PBS injection and sham operation group.

RESULTS: In the PAS staining, the ceria-nanoparticles showed protective effects in histologic changes in a dose-dependent manners (P<0.001). Relative activity of cleaved caspase-3 in kidney was significantly decreased in ceria-nanoparticle injection group compared with IRI alone and PBS injection group (P<0.01). HSP70 was also significantly decreased in rats with high dose ceria-nanoparticle injection. As for the mechanism of decreased IRI, reduced iNOS activity was evidenced in western blot. Relative activity of Toll-like receptor (TLR) 2 and 4 were significantly lower in ceria-nanoparticle injection group compared with IRI group and PBS injection group in a dose-dependent manners (P<0.01).

CONCLUSION: ceria-nanoparticles could prevent renal IRI by reducing oxidative stress in a rat kidney IRI model. In addition, deceasing activity of TLR2 and TLR4 would have an implication of protecting adaptive immunity. Further studies are needed to determine the accurate role in development of acute rejection.

CITATION INFORMATION: Min S-.I., Kim S., Kim S., Ha J. Protective Effect of Ceria-Nanoparticle on Renal Ischemia Reperfusion Injury in Rats Am J Transplant. 2017;17 (suppl 3).

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