摘要

Haemorrhagic shock and resuscitation (HS/R) may cause global ischaemia‐reperfusion injury, which can result in systemic inflammation, multiorgan failure (particularly liver failure) and high mortality. Hinokitiol, a bioactive tropolone‐related compound, exhibits antiplatelet and anti‐inflammatory activities. Targeting inflammatory responses is a potential strategy for ameliorating hepatic injury during HS/R. Whether hinokitiol prevents hepatic injury during HS/R remains unclear. In the present study, we determined the role of hinokitiol following HS/R. The in vivo assays revealed that hinokitiol markedly attenuated HS/R‐induced hepatic injury. Hinokitiol could inhibited NF‐κB activation and IL‐6 and TNF‐α upregulation in liver tissues. Moreover, hinokitiol reduced caspase‐3 activation, upregulated Bax and downregulated Bcl‐2. These findings suggest that hinokitiol can ameliorate liver injury following HS/R, partly through suppression of inflammation and apoptosis. Furthermore, the in vitro data revealed that hinokitiol significantly reversed hypoxia/reoxygenation (H/R)‐induced cell death and apoptosis in the primary hepatocytes. Hinokitiol prevented H/R‐induced caspase‐3 activation, PPAR cleavage, Bax overexpression and Bcl‐2 downregulation. Moreover, hinokitiol attenuated H/R‐stimulated NF‐κB activation and reduced the levels of IL‐6 and TNF‐α mRNAs, suggesting that hinokitiol can protect hepatocytes from H/R injury. Collectively, our data suggest that hinokitiol attenuates liver injury following HS/R, partly through the inhibition of NF‐κB activation.
原文英語
頁(從 - 到)1723-1734
頁數12
期刊Journal of Cellular and Molecular Medicine
23
發行號3
DOIs
出版狀態已發佈 - 三月 1 2019

指紋

Hemorrhagic Shock
Liver
Wounds and Injuries
Resuscitation
Therapeutics
Caspase 3
beta-thujaplicin
Hepatocytes
Interleukin-6
Down-Regulation
Tropolone
Apoptosis
Inflammation
Peroxisome Proliferator-Activated Receptors
Liver Failure
Reperfusion Injury
Cell Death
Anti-Inflammatory Agents
Up-Regulation

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

引用此文

@article{4ea982122d3745a4bb0fc75bb11fad4a,
title = "New therapeutic strategy of hinokitiol in haemorrhagic shock-induced liver injury",
abstract = "Haemorrhagic shock and resuscitation (HS/R) may cause global ischaemia-reperfusion injury, which can result in systemic inflammation, multiorgan failure (particularly liver failure) and high mortality. Hinokitiol, a bioactive tropolone-related compound, exhibits antiplatelet and anti-inflammatory activities. Targeting inflammatory responses is a potential strategy for ameliorating hepatic injury during HS/R. Whether hinokitiol prevents hepatic injury during HS/R remains unclear. In the present study, we determined the role of hinokitiol following HS/R. The in vivo assays revealed that hinokitiol markedly attenuated HS/R-induced hepatic injury. Hinokitiol could inhibited NF-κB activation and IL-6 and TNF-α upregulation in liver tissues. Moreover, hinokitiol reduced caspase-3 activation, upregulated Bax and downregulated Bcl-2. These findings suggest that hinokitiol can ameliorate liver injury following HS/R, partly through suppression of inflammation and apoptosis. Furthermore, the in vitro data revealed that hinokitiol significantly reversed hypoxia/reoxygenation (H/R)-induced cell death and apoptosis in the primary hepatocytes. Hinokitiol prevented H/R-induced caspase-3 activation, PPAR cleavage, Bax overexpression and Bcl-2 downregulation. Moreover, hinokitiol attenuated H/R-stimulated NF-κB activation and reduced the levels of IL-6 and TNF-α mRNAs, suggesting that hinokitiol can protect hepatocytes from H/R injury. Collectively, our data suggest that hinokitiol attenuates liver injury following HS/R, partly through the inhibition of NF-κB activation.",
keywords = "Hemorrhagic shock, hinokitiol, liver, resuscitation, trauma",
author = "Wan-Jung Lu and Kuan-Hung Lin and Mei-Fang Tseng and Kuo-Ching Yuan and Hung-Chang Huang and Joen-Rong Sheu and Ray-Jade Chen",
note = "{\circledC} 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.",
year = "2019",
month = "3",
day = "1",
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language = "English",
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TY - JOUR

T1 - New therapeutic strategy of hinokitiol in haemorrhagic shock-induced liver injury

AU - Lu, Wan-Jung

AU - Lin, Kuan-Hung

AU - Tseng, Mei-Fang

AU - Yuan, Kuo-Ching

AU - Huang, Hung-Chang

AU - Sheu, Joen-Rong

AU - Chen, Ray-Jade

N1 - © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Haemorrhagic shock and resuscitation (HS/R) may cause global ischaemia-reperfusion injury, which can result in systemic inflammation, multiorgan failure (particularly liver failure) and high mortality. Hinokitiol, a bioactive tropolone-related compound, exhibits antiplatelet and anti-inflammatory activities. Targeting inflammatory responses is a potential strategy for ameliorating hepatic injury during HS/R. Whether hinokitiol prevents hepatic injury during HS/R remains unclear. In the present study, we determined the role of hinokitiol following HS/R. The in vivo assays revealed that hinokitiol markedly attenuated HS/R-induced hepatic injury. Hinokitiol could inhibited NF-κB activation and IL-6 and TNF-α upregulation in liver tissues. Moreover, hinokitiol reduced caspase-3 activation, upregulated Bax and downregulated Bcl-2. These findings suggest that hinokitiol can ameliorate liver injury following HS/R, partly through suppression of inflammation and apoptosis. Furthermore, the in vitro data revealed that hinokitiol significantly reversed hypoxia/reoxygenation (H/R)-induced cell death and apoptosis in the primary hepatocytes. Hinokitiol prevented H/R-induced caspase-3 activation, PPAR cleavage, Bax overexpression and Bcl-2 downregulation. Moreover, hinokitiol attenuated H/R-stimulated NF-κB activation and reduced the levels of IL-6 and TNF-α mRNAs, suggesting that hinokitiol can protect hepatocytes from H/R injury. Collectively, our data suggest that hinokitiol attenuates liver injury following HS/R, partly through the inhibition of NF-κB activation.

AB - Haemorrhagic shock and resuscitation (HS/R) may cause global ischaemia-reperfusion injury, which can result in systemic inflammation, multiorgan failure (particularly liver failure) and high mortality. Hinokitiol, a bioactive tropolone-related compound, exhibits antiplatelet and anti-inflammatory activities. Targeting inflammatory responses is a potential strategy for ameliorating hepatic injury during HS/R. Whether hinokitiol prevents hepatic injury during HS/R remains unclear. In the present study, we determined the role of hinokitiol following HS/R. The in vivo assays revealed that hinokitiol markedly attenuated HS/R-induced hepatic injury. Hinokitiol could inhibited NF-κB activation and IL-6 and TNF-α upregulation in liver tissues. Moreover, hinokitiol reduced caspase-3 activation, upregulated Bax and downregulated Bcl-2. These findings suggest that hinokitiol can ameliorate liver injury following HS/R, partly through suppression of inflammation and apoptosis. Furthermore, the in vitro data revealed that hinokitiol significantly reversed hypoxia/reoxygenation (H/R)-induced cell death and apoptosis in the primary hepatocytes. Hinokitiol prevented H/R-induced caspase-3 activation, PPAR cleavage, Bax overexpression and Bcl-2 downregulation. Moreover, hinokitiol attenuated H/R-stimulated NF-κB activation and reduced the levels of IL-6 and TNF-α mRNAs, suggesting that hinokitiol can protect hepatocytes from H/R injury. Collectively, our data suggest that hinokitiol attenuates liver injury following HS/R, partly through the inhibition of NF-κB activation.

KW - Hemorrhagic shock

KW - hinokitiol

KW - liver

KW - resuscitation

KW - trauma

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U2 - 10.1111/jcmm.14070

DO - 10.1111/jcmm.14070

M3 - Article

VL - 23

SP - 1723

EP - 1734

JO - Journal of Cellular and Molecular Medicine

JF - Journal of Cellular and Molecular Medicine

SN - 1582-1838

IS - 3

ER -