• nanoceria

The combined approach of ex-situ normothermic machine perfusion and nanotechnology represents a new strategy to mitigate ischemia-reperfusion injury in liver transplantation. We evaluated the uptake, distribution, and efficacy of antioxidant cerium-oxide nanoparticles (nanoceria) during normothermic perfusion of discarded human livers. Nine discarded human liver grafts were randomized in two groups and underwent 4 hours NMP: 5 grafts were treated with nanoceria conjugated with albumin (Alb-NC,50 μmol/L) and compared to 4 untreated grafts. The intracellular uptake of nanoceria was analyzed by electron microscopy and inductively coupled plasma-mass spectrometry (ICP-MS). The antioxidant activity of Alb-NC was assayed in liver biopsies by glutathione, superoxide dismutase and catalase assay, telomere length and mitochondrial DNA deletion (mtDNA4977). Cytokine profile was evaluated in perfusate samples. Electron microscopy and ICP-MS confirmed Alb-NC internalization, rescue of mitochondrial phenotype, decrease of lipid droplet peroxidation and lipofuscin granules in the treated grafts. Alb-NC exerted an antioxidant activity by increasing glutathione levels (%change: +94%±25%;P=0.007), superoxide dismutase (+17%±4%;P=0.016) and catalase activity (51%±23;P=0.027), reducing the occurrence of mtDNA4977 deletion (-67.2%±11%;P=0.035), but did not affect cytokine release. Alb-NC during ex-situ perfusion decrease oxidative stress upregulating graft antioxidant defense. They could be an effective therapeutic tool to improve graft quality before transplantation.