Z Gastroenterol 2018; 56(05): e39
DOI: 10.1055/s-0038-1654636
POSTER
Hepatologie
Georg Thieme Verlag KG Stuttgart · New York

Alpha-1 antitrypsin administration ameliorates experimental acute alcoholic liver disease

C Grander
1   Medizinische Universität Innsbruck, Innere Medizin I, Gastroenterologie, Endokrinologie und Stoffwechsel, Innsbruck, Austria
,
B Schäfer
1   Medizinische Universität Innsbruck, Innere Medizin I, Gastroenterologie, Endokrinologie und Stoffwechsel, Innsbruck, Austria
,
F Grabherr
1   Medizinische Universität Innsbruck, Innere Medizin I, Gastroenterologie, Endokrinologie und Stoffwechsel, Innsbruck, Austria
,
B Enrich
1   Medizinische Universität Innsbruck, Innere Medizin I, Gastroenterologie, Endokrinologie und Stoffwechsel, Innsbruck, Austria
,
H Tilg
1   Medizinische Universität Innsbruck, Innere Medizin I, Gastroenterologie, Endokrinologie und Stoffwechsel, Innsbruck, Austria
› Author Affiliations
Further Information

Publication History

Publication Date:
09 May 2018 (online)

 

Background and Aims:

Alcoholic liver disease (ALD) represents the hepatic manifestation of alcohol overconsumption and includes a clinical spectrum ranging from alcoholic fatty liver, alcoholic steatohepatitis, progressive liver fibrosis to cirrhosis and hepatocellular carcinoma. Hence, blockage of anti-inflammatory pathways is seen as a promising therapeutic approach in ALD. Alpha-1 antitrypsin (A1AT) is a hepatic acute-phase protein and a well-known inhibitor of neutrophilic elastase function. We therefore aimed to analyse the effect of A1AT administration in a murine model of acute ALD.

Method:

Female C57BL/6 mice were gavaged with 5 g ethanol per kg bodyweight or isocaloric maltose solution. In a further experiment, mice were pre-treated with A1AT (0.5 mg per mouse) or vehicle (PBS) 48h, 24h and 1h before ethanol administration. Eight hours after ethanol gavage mice were sacrificed and tissue samples were harvested.

Results:

Administration of ethanol alone led to increased transaminase levels (p < 0.05) and enhanced hepatic expression of Tnf-a (p < 0.001) and Serpina-1 (A1AT; p < 0.01). Pre-treatment with A1AT reduced the hepatic mRNA expression profile of Tnf-a (p < 0.05), which was accompanied by trends towards decreased serum Tnf-a levels (p = 0,168). Additionally, A1AT led to decreased hepcidin expression in the liver (p < 0.05). Moreover, A1AT pre-treatment significantly reduced ethanol induced microvascular steatosis (p < 0.05).

Conclusion:

Our data indicate a possible protective role for A1AT in acute alcoholic liver disease.