ArticlePloS one2017
Levosimendan protects human hepatocytes from ischemia-reperfusion injury.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Perioperative Use of Levosimendan in Hepatic Transplantation With Diastolic Heart Failure: A Case Report.Cureus · 2024Article
- Levosimendan Increases Survival in a D-Galactosamine and Lipopolysaccharide Rat Model.Biomedicines · 2022Article
- The effect of post-reperfusion levosimendan in an experimental intestinal ischemia-reperfusion model.Journal of anesthesia, analgesia and critical care · 2022Article
- Targeted Mitochondrial Drugs for Treatment of Ischemia-Reperfusion Injury.Current drug targets · 2022Review
- Intranasal levosimendan prevents cognitive dysfunction and apoptotic response induced by repeated isoflurane exposure in newborn rats.Naunyn-Schmiedeberg's archives of pharmacology · 2021Article
- Exercise Capacity Is Improved by Levosimendan in Heart Failure and Sarcopenia via Alleviation of Apoptosis of Skeletal Muscle.Frontiers in physiology · 2021Article
- Multiorgan Drug Action of Levosimendan in Critical Illnesses.BioMed research international · 2019Review
- Use of Levosimendan in Intensive Care Unit Settings: An Opinion Paper.Journal of cardiovascular pharmacology · 2019Review
- Barriers and Advances in Kidney Preservation.BioMed research international · 2018Review
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIschemia-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.
methodsPrimary 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.
resultsAdministration 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.
conclusionThe 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.
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