TY  - JOUR
A1  - Brunner, Stefanie N.
A1  - Bogert, Nicolai Valentin
A1  - Schnitzbauer, Andreas
A1  - Jüngel, Eva
A1  - Moritz, Anton
A1  - Werner, Isabella
A1  - Kornberger, Angela
A1  - Beiras Fernández, Andrés
T1  - Levosimendan protects human hepatocytes from ischemia-reperfusion injury
T2  - PLoS one
N2  - 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.
KW  - Hepatocytes
KW  - Apoptosis
KW  - Reperfusion
KW  - Liver transplantation
KW  - MTT assay
KW  - Cell metabolism
KW  - Mitochondria
KW  - Heart failure
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/44363
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-443637
SN  - 1932-6203
N1  - Copyright: © 2017 Brunner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
VL  - 12
IS  - (11): e0187839
SP  - 1
EP  - 11
PB  - PLoS
CY  - Lawrence, Kan.
ER  -