Z Gastroenterol 2012; 50 - P1_47
DOI: 10.1055/s-0031-1295779

Human augmenter of liver regeneration could have a potential protective role in an alcohol-induced toxicity model

C Schelcher 1, S Lee 1, C Casey 2, S Gashi 3, KW Jauch 1, WE Thasler 1
  • 1Department of Surgery, Großhadern Hospital, Ludwig Maximilians University, Munich
  • 2University of Nebraska Medical Center and Veterans Affairs Medical Center, Omaha, USA
  • 3Tissue Bank under the Authority of the Human Tissue and Cell Research (HTCR) Foundation, Großhadern Hospital, Munich

Background Alcoholic liver disease (ALD) is a major health problem worldwide and development of a therapeutical agent that could enhance protection against apoptosis would facilitate the treatment of ALD. The augmenter of liver regeneration (ALR) was originally discovered as a key protein in liver regeneration and more recently studies have found that ALR also protects against cell death caused by various apoptotic stimuli. ALR has two isoforms; the full-length isoform (fALR) is localised in the inter-membrane space of the mitochondrion, while the truncated isoform (tALR) is a circulating cytokine. However, the protective role of ALR against ethanol-induced toxicity is not known at present. Therefore, this study aimed to characterise the expression level of ALR and the protein content of both isoforms in an ethanol-induced toxicity model.

Methods Male Wistar rats were sacrificed for liver collection after being pair-fed for 8 weeks with Lieber-DeCarli control or ethanol diet. Serum was extracted from blood samples and used to determine the activity of Alanine Transaminase in control (n=4) and ethanol fed rats (n=4). Gene expression was measured by real time PCR and western blot analyses performed on RNA and protein extracted from the livers of ethanol fed rats (n=10) and control rats (n=10).

Results Following the feeding for 8 weeks, ethanol treatment has been shown to significantly increase apoptosis and necrosis. Coincident with the above results, the mRNA level of ALR has been found to be significantly decreased by 31% following ethanol treatment. Interestingly, the protein level of fALR was not significantly changed by ethanol treatment compared to the control, whilst there was a significant downregulation of the tALR by 42%.

Conclusion This study showed for the first time that ALR is deficient in a model of ethanol-induced toxicity. We could therefore potentially use ALR as a therapeutic agent, which could slow or prevent ALD progression.

ALR - Alcoholic liver disease - Augmenter of liver regeneration - Liver regeneration - apoptosis