Bilirubin nanoparticle preconditioning protects against hepatic ischemia-reperfusion injury

Jin Yong Kim, Dong Yun Lee, Sukmo Kang, Wenjun Miao, Hyungjun Kim, Yonghyun Lee, Sangyong Jon

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalBiomaterials
Volume133
DOIs
StatePublished - 1 Jul 2017

Keywords

  • Anti-inflammatory therapy
  • Bilirubin
  • Ischemia-reperfusion injury
  • Liver transplantation
  • Nanoparticles
  • Reactive oxygen species

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