Bilirubin nanoparticle preconditioning protects against hepatic ischemia-reperfusion injury

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Hepatic ischemia-reperfusion injury (IRI) remains a major concern in liver transplantation and resection, despite continuing efforts to prevent it. Accumulating evidence suggests that bilirubin possesses antioxidant, anti-inflammatory and anti-apoptotic properties. However, despite obvious potential health benefits of bilirubin, its clinical applications are limited by its poor solubility. We recently developed bilirubin nanoparticles (BRNPs) consisting of polyethylene glycol (PEG)-conjugated bilirubin. Here, we sought to investigate whether BRNPs protect against IRI in the liver by preventing oxidative stress. BRNPs exerted potent antioxidant and anti-apoptotic activity in primary hepatocytes exposed to hydrogen peroxide, a precursor of reactive oxygen species (ROS). In a model of hepatic IRI in mice, BRNP preconditioning exerted profound protective effects against hepatocellular injury by reducing oxidative stress, pro-inflammatory cytokine production, and recruitment of neutrophils. They also preferentially accumulated in IRI-induced inflammatory lesions. Collectively, our findings indicate that BRNP preconditioning provides a simple and safe approach that can be easily monitored in the blood like endogenous bilirubin, and could be a promising strategy to protect against IRI in a clinical setting. (C) 2017 Elsevier Ltd. All rights reserved.
Publisher
ELSEVIER SCI LTD
Issue Date
2017-07
Language
English
Article Type
Article
Keywords

LIVER-TRANSPLANTATION; REACTIVE OXYGEN; ANTIOXIDANT; STRATEGIES; THERAPY; DISEASE

Citation

BIOMATERIALS, v.133, pp.1 - 10

ISSN
0142-9612
DOI
10.1016/j.biomaterials.2017.04.011
URI
http://hdl.handle.net/10203/224039
Appears in Collection
BS-Journal Papers(저널논문)
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