Cerium oxide nanoparticles administration during machine perfusion of discarded human livers: A pilot study

被引:22
作者
Del Turco, Serena [1 ]
Cappello, Valentina [2 ]
Tapeinos, Christos [3 ]
Moscardini, Aldo [4 ]
Sabatino, Laura [1 ]
Battaglini, Matteo [3 ]
Melandro, Fabio [5 ]
Torri, Francesco [5 ]
Martinelli, Caterina [5 ]
Babboni, Serena [1 ]
Silvestrini, Beatrice [6 ]
Morganti, Riccardo [7 ]
Gemmi, Mauro [2 ]
De Simone, Paolo [5 ]
Martins, Paulo N. [8 ]
Crocetti, Laura [6 ]
Peris, Adriano [9 ]
Campani, Daniela [10 ]
Basta, Giuseppina [1 ]
Ciofani, Gianni [3 ]
Ghinolfi, Davide [5 ]
机构
[1] CNR, Inst Clin Physiol, Via Moruzzi, I-156124 Pisa, Italy
[2] Ist Italiano Tecnol, Ctr Mat Interfaces, Electron Crystallog, Pontedera, Italy
[3] Ist Italiano Tecnol, Smart Biointerfaces, Pontedera, Italy
[4] Scuola Normale Super Pisa, Natl Enterprise NanoSci & NanoTechnol, Pisa, Italy
[5] Univ Pisa, Div Hepat Surg & Liver Transplantat, Med Sch Hosp, Via Paradisa 2, I-56124 Pisa, Italy
[6] Univ Pisa, Div Intervent Radiol, Med Sch Hosp, Pisa, Italy
[7] Univ Pisa, Dept Stat, Pisa, Italy
[8] Univ Massachusetts, Dept Surg, Div Transplantat, Worcester, MA 01605 USA
[9] Reg Transplant Author Tuscany, Florence, Italy
[10] Univ Pisa, Div Pathol, Med Sch Hosp, Pisa, Italy
关键词
ISCHEMIA-REPERFUSION INJURY; TRANSPLANTATION;
D O I
10.1002/lt.26421
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
The combined approach of ex situ normothermic machine perfusion (NMP) and nanotechnology represents a strategy to mitigate ischemia/reperfusion injury in liver transplantation (LT). We evaluated the uptake, distribution, and efficacy of antioxidant cerium oxide nanoparticles (nanoceria) during normothermic perfusion of discarded human livers. A total of 9 discarded human liver grafts were randomized in 2 groups and underwent 4 h of NMP: 5 grafts were treated with nanoceria conjugated with albumin (Alb-NC; 50 mu g/ml) and compared with 4 untreated grafts. The intracellular uptake of nanoceria was analyzed by electron microscopy (EM) and inductively coupled plasma-mass spectrometry (ICP-MS). The antioxidant activity of Alb-NC was assayed in liver biopsies by glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) assay, telomere length, and 4977-bp common mitochondrial DNA deletion (mtDNA(4977) deletion). The cytokine profile was evaluated in perfusate samples. EM 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 GSH levels (percentage change: +94% +/- 25%; p = 0.01), SOD (+17% +/- 4%; p = 0.02), and CAT activity (51% +/- 23%; p = 0.03), reducing the occurrence of mtDNA(4977) deletion (-67.2% +/- 11%; p = 0.03), but did not affect cytokine release. Alb-NC during ex situ perfusion decreased oxidative stress, upregulating graft antioxidant defense. They could be a tool to improve quality grafts during NMP and represent an antioxidant strategy aimed at protecting the graft against reperfusion injury during LT.
引用
收藏
页码:1173 / 1185
页数:13
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