gms | German Medical Science

128. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

03.05. - 06.05.2011, München

Hepatic protection of growth factors against ethanol toxicity

Meeting Abstract

  • Maren Ilowski - Liver regeneration group, Department of Surgery, Grosshadern Hospital, Ludwig Maximilians University, Munich
  • Serene Lee - Liver regeneration group, Department of Surgery, Grosshadern Hospital, Ludwig Maximilians University, Munich
  • Markus Rentsch - Department of Surgery, Grosshadern Hospital, Ludwig Maximilians University, Munich
  • Karl-Walter Jauch - Universitätsklinikum der LMU München-Großhadern, Chirurgische Klinik und Poliklinik, Munich
  • Wolfgang Thasler - Liver regeneration group, Department of Surgery, Grosshadern Hospital, Ludwig Maximilians University, Munich

Deutsche Gesellschaft für Chirurgie. 128. Kongress der Deutschen Gesellschaft für Chirurgie. München, 03.-06.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. Doc11dgch205

DOI: 10.3205/11dgch205, URN: urn:nbn:de:0183-11dgch2057

Veröffentlicht: 20. Mai 2011

© 2011 Ilowski et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Introduction: The liver is a highly metabolic organ with a great potential of regeneration. Besides mitogenic signals via growth factors, liver regeneration is also triggered by metabolites and anti-apoptotic mechanisms. The aim of this study was to investigate a possible protective effect of growth factors in vitro against ethanol administration. Growth factors of interest include augmenter of liver regeneration (ALR), epidermal growth factor (EGF) and hepatocyte growth factor (HGF).

Materials and methods: Primary human hepatocytes (phH) and hepatic cell lines were exposed to different concentrations of ethanol in the presence or absence of the growth factors. The influence on cell proliferation was analyzed by MTT assay. As an indicator of irreversible cell death, the percent leakage of intracellular LDH into the culture medium was measured. The amount of ethanol-induced apoptosis was evaluated by FACS analysis with propidium iodide (PI) staining and oxidative stress was gauged by measuring the GSH/GSSG ratio. Selected proteins of the above signal pathways were analyzed by Western Blot.

Results: Pre-incubation of cells with recombinant human ALR, EGF and HGF resulted in an increased in proliferation of HepG2 cells and primary human hepatocytes. The collected data revealed a concentration dependent increase in cell damage induced by ethanol as well as a protective effect of rhALR (FACS analysis, enzyme leakage). The phosphorylation of Akt, an important survival signal, was activated by rhALR. Compared to EGF and HGF, the hepatotrophic growth factor rhALR acts in a liver specific manner with regards to both its mitogenic and protective effect.

Conclusion: Unlike growth factors like HGF and EGF, rhALR acts in a liver specific manner and shows not only mitogenic but also protective effects through the PI3K/AKT signaling pathway against ethanol toxicity. Thus, ALR administration can potentially provide liver specific protection and also support liver regeneration.