Bilirubin nanoparticle preconditioning protects against hepatic ischemia-reperfusion injury
Bilirubin nanoparticle preconditioning protects against hepatic ischemia-reperfusion injury
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DOI：
10.1016/j.biomaterials.2017.04.011
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发表时间：
2017-07-01
期刊：
影响因子：
14
通讯作者：
Jon, Sangyong
中科院分区：
文献类型：
--
作者：
Kim, Jin Yong;Lee, Dong Yun;Jon, Sangyong
肝缺血再灌注损伤（IRI）是肝移植和肝切除术中的一个主要问题，尽管人们一直在努力预防它的发生。越来越多的证据表明胆红素具有抗氧化、抗炎和抗凋亡的特性。然而，尽管胆红素具有明显的潜在健康益处，但其溶解度差限制了其临床应用。我们最近开发了由聚乙二醇（PEG）结合胆红素组成的胆红素纳米颗粒（BRNPs）。在这里，我们试图研究BRNP是否通过防止氧化应激来保护肝脏免受IRI。BRNP在暴露于过氧化氢（活性氧（ROS）的前体）的原代肝细胞中发挥了有效的抗氧化和抗凋亡活性。在小鼠肝脏IRI模型中，BRNP预处理通过减少氧化应激、促炎细胞因子产生和中性粒细胞募集对肝细胞损伤产生深远的保护作用。它们也优先在IRI诱导的炎性病变中积累。总的来说，我们的研究结果表明，BRNP预处理提供了一种简单而安全的方法，可以像内源性胆红素一样在血液中容易地监测，并且可能是一种有前途的策略，以防止在临床环境中的IRI。(C)2017爱思唯尔有限公司版权所有
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.