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Short-term treatment with taurolidine is associated with liver injury

BACKGROUND: Taurolidine has been used for peritonitis, oncological and catheter-lock treatment because of its anti-inflammatory properties. It has been suggested that taurolidine has no severe side-effects, but after long-term use morphological and functional changes of the liver were reported. The...

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Autores principales: Fahrner, René, Möller, Anika, Press, Adrian T., Kortgen, Andreas, Kiehntopf, Michael, Rauchfuss, Falk, Settmacher, Utz, Mosig, Alexander S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5553585/
https://www.ncbi.nlm.nih.gov/pubmed/28800748
http://dx.doi.org/10.1186/s40360-017-0168-z
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author Fahrner, René
Möller, Anika
Press, Adrian T.
Kortgen, Andreas
Kiehntopf, Michael
Rauchfuss, Falk
Settmacher, Utz
Mosig, Alexander S.
author_facet Fahrner, René
Möller, Anika
Press, Adrian T.
Kortgen, Andreas
Kiehntopf, Michael
Rauchfuss, Falk
Settmacher, Utz
Mosig, Alexander S.
author_sort Fahrner, René
collection PubMed
description BACKGROUND: Taurolidine has been used for peritonitis, oncological and catheter-lock treatment because of its anti-inflammatory properties. It has been suggested that taurolidine has no severe side-effects, but after long-term use morphological and functional changes of the liver were reported. The aim of this study was to investigate the effect of short-term use of taurolidine on the liver. METHODS: In HepaRG cell cultures and on a novel liver biochip dose-dependent effects of taurolidine treatment on hepatocyte adherence and cell viability was investigated. Furthermore, liver enzymes and interleukin- (IL-) 6 were measured in supernatants. Male rats were treated with low- or high-dose taurolidine, respectively, and compared to controls with physiological saline solution administration regarding blood serum parameters and histology. RESULTS: In HepaRG cell cultures, hepatocyte adherence was significantly decreased, cell death and cleaved caspase-3 were significantly increased after administration of taurolidine in a dose-dependent manner. High-dose application of taurolidine led to elevated liver enzymes and IL-6 secretion in hepatic organoid. After 24 h a significant increase of serum GLDH and ASAT was observed in rats treated with high-dose taurolidine treatment. CONCLUSIONS: Our results suggest that taurolidine caused liver injury after short-term use in in vitro and in vivo models probably due to direct toxic effects on hepatocytes. Therefore, the taurolidine dose should be titrated in further investigations regarding liver injury and inflammation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40360-017-0168-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-55535852017-08-15 Short-term treatment with taurolidine is associated with liver injury Fahrner, René Möller, Anika Press, Adrian T. Kortgen, Andreas Kiehntopf, Michael Rauchfuss, Falk Settmacher, Utz Mosig, Alexander S. BMC Pharmacol Toxicol Research Article BACKGROUND: Taurolidine has been used for peritonitis, oncological and catheter-lock treatment because of its anti-inflammatory properties. It has been suggested that taurolidine has no severe side-effects, but after long-term use morphological and functional changes of the liver were reported. The aim of this study was to investigate the effect of short-term use of taurolidine on the liver. METHODS: In HepaRG cell cultures and on a novel liver biochip dose-dependent effects of taurolidine treatment on hepatocyte adherence and cell viability was investigated. Furthermore, liver enzymes and interleukin- (IL-) 6 were measured in supernatants. Male rats were treated with low- or high-dose taurolidine, respectively, and compared to controls with physiological saline solution administration regarding blood serum parameters and histology. RESULTS: In HepaRG cell cultures, hepatocyte adherence was significantly decreased, cell death and cleaved caspase-3 were significantly increased after administration of taurolidine in a dose-dependent manner. High-dose application of taurolidine led to elevated liver enzymes and IL-6 secretion in hepatic organoid. After 24 h a significant increase of serum GLDH and ASAT was observed in rats treated with high-dose taurolidine treatment. CONCLUSIONS: Our results suggest that taurolidine caused liver injury after short-term use in in vitro and in vivo models probably due to direct toxic effects on hepatocytes. Therefore, the taurolidine dose should be titrated in further investigations regarding liver injury and inflammation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40360-017-0168-z) contains supplementary material, which is available to authorized users. BioMed Central 2017-08-11 /pmc/articles/PMC5553585/ /pubmed/28800748 http://dx.doi.org/10.1186/s40360-017-0168-z Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Fahrner, René
Möller, Anika
Press, Adrian T.
Kortgen, Andreas
Kiehntopf, Michael
Rauchfuss, Falk
Settmacher, Utz
Mosig, Alexander S.
Short-term treatment with taurolidine is associated with liver injury
title Short-term treatment with taurolidine is associated with liver injury
title_full Short-term treatment with taurolidine is associated with liver injury
title_fullStr Short-term treatment with taurolidine is associated with liver injury
title_full_unstemmed Short-term treatment with taurolidine is associated with liver injury
title_short Short-term treatment with taurolidine is associated with liver injury
title_sort short-term treatment with taurolidine is associated with liver injury
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5553585/
https://www.ncbi.nlm.nih.gov/pubmed/28800748
http://dx.doi.org/10.1186/s40360-017-0168-z
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