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Liver transplantation (LT), an ultimate and vital method for treating end-stage liver disease, is often accompanied by ischemia-reperfusion injury (IRI) resulting from warm or cold ischemia of the donor liver. Organ protection techniques are used to improve the quality of liver grafts (from retrieval to implantation). Reactive oxygen species (ROS) cause oxidative stress, which is considered a crucial factor in IRI after LT. Nano antioxidants capable of scavenging ROS alleviate IRI in multiple types of organs and tissues. In this study, we synthesized ceria nanoparticles (NPs) with antioxidant properties using a pyrolysis method and covered them with phospholipid-polyethylene glycol to improve their biocompatibility in vivo. We investigated the potential organ-protective effect of ceria NPs and the underlying mechanisms. Ceria NPs promoted liver function recovery after LT by attenuating IRI in liver grafts in vivo. The protective effect of ceria NPs on liver grafts was investigated by applying hypothermic oxygenated machine perfusion ex vivo. Ceria NPs attenuated hypoxia reoxygenation- or H2O2-induced hepatocyte injury by enhancing mitochondrial activity and ROS scavenging in vitro. These effects may be associated with the activation of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)/heme oxygenase 1 (HO-1) signaling pathway. In conclusion, ceria NPs may serve as a promising antioxidant agent for the treatment of hepatic IRI after LT.


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Application of biocompatible custom ceria nanoparticles in improving the quality of liver grafts for transplantation

Show Author's information Yinbiao Qiao1,2,§Jianhui Li2,3,4,§Suchen Bian1,2Chenyue Zhan1Jia Luo1,2Li Jiang1,2Haoyu Li2Hao Wu1Cheng Zhang1Shusen Zheng1,2 ( )Haiyang Xie1,2( )Penghong Song1,2( )
Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
National Health Commission (NHC) Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China
Department of Hepatobiliary and Pancreatic Surgery, Department of Liver Transplantation, Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, Hangzhou 310015, China
The Organ Repair and Regeneration Medicine Institute of Hangzhou, Hangzhou 310003, China

§ Yinbiao Qiao and Jianhui Li contributed equally to this work.

Abstract

Liver transplantation (LT), an ultimate and vital method for treating end-stage liver disease, is often accompanied by ischemia-reperfusion injury (IRI) resulting from warm or cold ischemia of the donor liver. Organ protection techniques are used to improve the quality of liver grafts (from retrieval to implantation). Reactive oxygen species (ROS) cause oxidative stress, which is considered a crucial factor in IRI after LT. Nano antioxidants capable of scavenging ROS alleviate IRI in multiple types of organs and tissues. In this study, we synthesized ceria nanoparticles (NPs) with antioxidant properties using a pyrolysis method and covered them with phospholipid-polyethylene glycol to improve their biocompatibility in vivo. We investigated the potential organ-protective effect of ceria NPs and the underlying mechanisms. Ceria NPs promoted liver function recovery after LT by attenuating IRI in liver grafts in vivo. The protective effect of ceria NPs on liver grafts was investigated by applying hypothermic oxygenated machine perfusion ex vivo. Ceria NPs attenuated hypoxia reoxygenation- or H2O2-induced hepatocyte injury by enhancing mitochondrial activity and ROS scavenging in vitro. These effects may be associated with the activation of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)/heme oxygenase 1 (HO-1) signaling pathway. In conclusion, ceria NPs may serve as a promising antioxidant agent for the treatment of hepatic IRI after LT.

Keywords: antioxidant, ceria nanoparticles, liver transplantation, hypothermic oxygenated machine perfusion (HOPE), ischemia-reperfusion injury (IRI)

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Publication history
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Acknowledgements

Publication history

Received: 02 August 2022
Revised: 19 September 2022
Accepted: 19 September 2022
Published: 23 November 2022
Issue date: April 2023

Copyright

© Tsinghua University Press 2022

Acknowledgements

Acknowledgements

This study was supported by Public Projects of Zhejiang Province (No. LGF21H030006), Major Science and Technology Projects of Hainan Province (No. ZDKJ2019009), the Zhejiang Provincial Natural Science Foundation of China (No. LZ21H180001), a Research Project of Jinan Microecological Biomedicine Shandong Laboratory (Nos. JNL-2022002A, JNL-2022007B, and JNL-2022023C), and the National Natural Science Foundation of China (No. 82000618).

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