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Anti-apoptotic therapeutic approaches in liver diseases: do they really make sense?

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Abstract

A variety of data suggesting apoptotic cell death as a key feature of liver injury stimulated researchers to investigate the therapeutic potential of anti-apoptotic strategies in experimental models. However, the overestimated role of apoptotic cell death in liver injury has tempered the clinical translation of the protection afforded by anti-apoptotic regimes in experimental models. Thus, the hope for apoptosis modulation as potential treatment strategy for injured liver in humans could not be confirmed. Herein, we evaluated the degree of apoptosis in different hepatic stress models which are relevant for the human pathophysiology. Using morphological criteria of apoptosis, caspase-3 activation as well as TUNEL assay in combination with a positive control of apoptosis in liver injury, we quantified apoptotic cell death discriminating between parenchymal and non-parenchymal cells and confirmed these results by cleaved caspase-3 and PARP-1 protein expression. Discussing our findings and relating them to the existing literature on the potential role of apoptotic cell death, we strongly recommend reconsidering anti-apoptotic strategies to ameliorate liver injury efficiently.

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Acknowledgments

This work was supported in part by the Deutsche Forschungsgemeinschaft, Bonn-Bad Godesberg, Germany (Ei 768/1-2; AB 453/1-1). The authors kindly thank Berit Blendow, Dorothea Frenz, Eva Lorbeer-Rehfeldt and Maren Nerowski (Institute for Experimental Surgery, University of Rostock) for excellent technical assistance.

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All authors declare that they have no conflicts of interest.

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  1. Institute for Experimental Surgery, Rostock University Medical School, Schillingallee 69 a, 18057, Rostock, Germany

    Karen Bannert, Angela Kuhla, Kerstin Abshagen & Brigitte Vollmar

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  1. Karen Bannert
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Correspondence to Kerstin Abshagen.

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Bannert, K., Kuhla, A., Abshagen, K. et al. Anti-apoptotic therapeutic approaches in liver diseases: do they really make sense?. Apoptosis 19, 1243–1253 (2014). https://doi.org/10.1007/s10495-014-1004-1

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