Format

Send to

Choose Destination
PLoS One. 2017 Nov 16;12(11):e0187839. doi: 10.1371/journal.pone.0187839. eCollection 2017.

Levosimendan protects human hepatocytes from ischemia-reperfusion injury.

Author information

1
Department of Thoracic and Cardiovascular Surgery, University Hospital Frankfurt, Goethe University, Frankfurt/Main, Germany.
2
Department of Cardiology, University Hospital Heidelberg, Ruprecht-Karls-University, Heidelberg, Germany.
3
Clinic for General and Visceral Surgery, University Hospital Frankfurt, Goethe University, Frankfurt/Main, Germany.
4
Department of Urology, University Hospital Mainz, Johannes Gutenberg University, Mainz, Germany.
5
Department of Thoracic and Cardiovascular Surgery, University Hospital Mainz, Johannes Gutenberg University, Mainz, Germany.

Abstract

BACKGROUND:

Ischemia-reperfusion injury (IRI) is a major challenge in liver transplantation. The mitochondrial pathway plays a pivotal role in hepatic IRI. Levosimendan, a calcium channel sensitizer, was shown to attenuate apoptosis after IRI in animal livers. The aim of this study was to investigate the effect of levosimendan on apoptosis in human hepatocytes.

METHODS:

Primary human hepatocytes were either exposed to hypoxia or cultured under normoxic conditions. After the hypoxic phase, reoxygenation was implemented and cells were treated with different concentrations of levosimendan (10ng/ml, 100ng/ml, 1000ng/ml). The overall metabolic activity of the cells was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and aspartate aminotransferase (AST) levels were determined in order to quantify hepatic injury. Fluorescence-activated cell sorting (FACS) analysis was applied to measure necrosis and apoptosis. Finally, Western blotting was performed to analyze apoptotic pathway proteins.

RESULTS:

Administration of levosimendan during reperfusion increases the metabolic activity of human hepatocytes and decreases AST levels. Moreover, apoptosis after IRI is reduced in treated vs. untreated hepatocytes, and levosimendan prevents down-regulation of the anti-apoptotic protein Bcl-2 as well as up-regulation of the pro-apoptotic protein BAX.

CONCLUSION:

The present study suggests a protective effect of levosimendan on human hepatocytes. Our findings suggest that treatment with levosimendan during reperfusion attenuates apoptosis of human hepatocytes by influencing BAX and Bcl-2 levels.

PMID:
29145424
PMCID:
PMC5690693
DOI:
10.1371/journal.pone.0187839
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center