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Induction of heme oxygenase-1 improves cold preservation effect of liver graft

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Abstract

We have examined the protective effect and mechanisms of heme oxygenase-1 (HO-1) induction in rat liver model of ex vivo cold ischemia preservation using cobalt protoporphyrin (CoPP) as HO-1 inducer and zinc protoporphyrin (ZnPP) as HO-1 inhibitor. There was a decrease in both aspartate transaminase and lactate dehydrogenase activities and in malondialdehyde level in liver of the CoPP-treated group compared with controls (p < 0.05). In the CoPP-treated rats, the histological signs of reperfusion injury were much lower than in control. Up-regulation of HO-1 expression was also associated with reduced levels of tumor necrosis factor α and interleukin-6. Markedly fewer apoptotic liver cells (determined by TUNEL assay) could be detected in CoPP-treated group compared with the control group. These protective effects were prevented by administration of ZnPP. In conclusion, induction of HO-1 provides protection against liver injury during cold ischemia preservation and improves the preservation of liver graft. The mechanisms underlying these beneficial effects include reduction of oxidative injury and of inflammatory response and prevention of apoptosis.

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Abbreviations

AST:

aspartate transaminase

CoPP:

cobalt protoporphyrin

HO:

heme oxygenases

IL-6:

interleukin-6

IRI:

ischemia/reperfusion injury

LDH:

lactate dehydrogenase

MDA:

malondialdehyde

TNF-α:

tumor necrosis factor α

TUNEL:

terminal deoxynucleotide transferase-mediated dUTP nick end labeling

UW solution:

University of Wisconsin solution

ZnPP:

zinc protoporphyrin

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Authors and Affiliations

  1. Institute of Transfusion Medicine, Academy of Military Medical Sciences, Beijing, 100850, China

    Liu Ming, Wang Bo, Zhao Xiaoyu, Wang Guangyi & Zhou Hong

  2. Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, 150086, China

    Liu Ming

Authors
  1. Liu Ming
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  2. Wang Bo
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  3. Zhao Xiaoyu
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  4. Wang Guangyi
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  5. Zhou Hong
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Correspondence to Zhou Hong.

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Published in Russian in Biokhimiya, 2007, Vol. 72, No. 5, pp. 674–681.

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Liu, M., Wang, B., Zhao, X. et al. Induction of heme oxygenase-1 improves cold preservation effect of liver graft. Biochemistry Moscow 72, 545–551 (2007). https://doi.org/10.1134/S0006297907050112

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  • DOI: https://doi.org/10.1134/S0006297907050112

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