Short-term treatment with taurolidine is associated with liver injury

René Fahrner,Falk Rauchfuss,Adrian T. Press,Michael Kiehntopf,Alexander S. Mosig,Utz Settmacher,Anika Möller,Andreas Kortgen

doi:10.1186/s40360-017-0168-z

René Fahrner, Falk Rauchfuss + Show 6 more

Open Access

https://doi.org/10.1186/s40360-017-0168-z

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Abstract

BackgroundTaurolidine 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.MethodsIn 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.ResultsIn 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.ConclusionsOur 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.

Highlights

Taurolidine has been used for peritonitis, oncological and catheter-lock treatment because of its anti-inflammatory properties
Taurolidine caused disruption of hepatic cell adherence and cell death in vitro HepaRG cells were treated with increasing doses of taurolidine in cell cultures
The release of liver enzymes in supernatants of cell cultures such as aspartate aminotransferase (ASAT) and glutamate dehydrogenase (GLDH) significantly correlated with increasing taurolidine concentrations (Fig. 1c and d)

Summary

Introduction

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. Taurolidine was reported to be a well-tolerated drug without relevant side effects in animal studies and in human local peritoneal and pleural application [11, 14, 15, 17, 28, 29]. The authors suggested caution before widespread use of taurolidine as an anti-cancer drug in clinical oncology [31]

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