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Alpha-1 Anti-trypsin Exerts a Hepatoprotective Effect on Immune-mediated Hepatitis and Acetaminophen-induced Liver Injury

Background and Aims: The serine proteinase inhibitor alpha-1 anti-trypsin (AAT) protects the body against protease activity. Several functions of AAT beyond those attributed to its anti-protease activity have been described, among them immunomodulatory and anti-inflammatory properties. The present s...

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Autores principales: Shabat, Yehudit, Ya’acov, Ami Ben, Ilan, Yaron
Formato: Online Artículo Texto
Lenguaje:English
Publicado: XIA & HE Publishing Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328735/
https://www.ncbi.nlm.nih.gov/pubmed/30637210
http://dx.doi.org/10.14218/JCTH.2018.00030
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author Shabat, Yehudit
Ya’acov, Ami Ben
Ilan, Yaron
author_facet Shabat, Yehudit
Ya’acov, Ami Ben
Ilan, Yaron
author_sort Shabat, Yehudit
collection PubMed
description Background and Aims: The serine proteinase inhibitor alpha-1 anti-trypsin (AAT) protects the body against protease activity. Several functions of AAT beyond those attributed to its anti-protease activity have been described, among them immunomodulatory and anti-inflammatory properties. The present study aimed to determine the efficacy of AAT for the treatment of immune-mediated liver injury using the models of concanavalin A-induced immune-mediated hepatitis and acetaminophen -induced liver damage. Methods: AAT was administered to mice subjected to concanavalin A-induced immune-mediated hepatitis or 2 h after acetaminophen-induced liver damage. Mice were followed for changes in serum levels of liver enzymes, liver histology, and for interferon gamma serum levels. Results: Treatment with AAT alleviated concanavalin A-induced immune-mediated liver damage, as demonstrated by a reduction in the serum levels of liver enzymes and interferon gamma, and an improved lymphocyte infiltration into the liver on liver biopsies. Moreover, treatment with AAT was associated with alleviation of the acetaminophen-induced liver injury. Conclusions: AAT exerts an hepatoprotective effect on immune-mediated and drug-induced liver damage. The data support its potential use in patients with immune-associated liver disorders.
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spelling pubmed-63287352019-01-11 Alpha-1 Anti-trypsin Exerts a Hepatoprotective Effect on Immune-mediated Hepatitis and Acetaminophen-induced Liver Injury Shabat, Yehudit Ya’acov, Ami Ben Ilan, Yaron J Clin Transl Hepatol Original Article Background and Aims: The serine proteinase inhibitor alpha-1 anti-trypsin (AAT) protects the body against protease activity. Several functions of AAT beyond those attributed to its anti-protease activity have been described, among them immunomodulatory and anti-inflammatory properties. The present study aimed to determine the efficacy of AAT for the treatment of immune-mediated liver injury using the models of concanavalin A-induced immune-mediated hepatitis and acetaminophen -induced liver damage. Methods: AAT was administered to mice subjected to concanavalin A-induced immune-mediated hepatitis or 2 h after acetaminophen-induced liver damage. Mice were followed for changes in serum levels of liver enzymes, liver histology, and for interferon gamma serum levels. Results: Treatment with AAT alleviated concanavalin A-induced immune-mediated liver damage, as demonstrated by a reduction in the serum levels of liver enzymes and interferon gamma, and an improved lymphocyte infiltration into the liver on liver biopsies. Moreover, treatment with AAT was associated with alleviation of the acetaminophen-induced liver injury. Conclusions: AAT exerts an hepatoprotective effect on immune-mediated and drug-induced liver damage. The data support its potential use in patients with immune-associated liver disorders. XIA & HE Publishing Inc. 2018-11-05 2018-12-28 /pmc/articles/PMC6328735/ /pubmed/30637210 http://dx.doi.org/10.14218/JCTH.2018.00030 Text en © 2018 Authors. http://creativecommons.org/licenses/by-nc/4.0/ This article has been published under the terms of Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0), which permits noncommercial unrestricted use, distribution, and reproduction in any medium, provided that the following statement is provided. “This article has been published in Journal of Clinical and Translational Hepatology at DOI: 10.14218/JCTH.2018.00030 and can also be viewed on the Journal’s website at http://www.jcthnet.com”.
spellingShingle Original Article
Shabat, Yehudit
Ya’acov, Ami Ben
Ilan, Yaron
Alpha-1 Anti-trypsin Exerts a Hepatoprotective Effect on Immune-mediated Hepatitis and Acetaminophen-induced Liver Injury
title Alpha-1 Anti-trypsin Exerts a Hepatoprotective Effect on Immune-mediated Hepatitis and Acetaminophen-induced Liver Injury
title_full Alpha-1 Anti-trypsin Exerts a Hepatoprotective Effect on Immune-mediated Hepatitis and Acetaminophen-induced Liver Injury
title_fullStr Alpha-1 Anti-trypsin Exerts a Hepatoprotective Effect on Immune-mediated Hepatitis and Acetaminophen-induced Liver Injury
title_full_unstemmed Alpha-1 Anti-trypsin Exerts a Hepatoprotective Effect on Immune-mediated Hepatitis and Acetaminophen-induced Liver Injury
title_short Alpha-1 Anti-trypsin Exerts a Hepatoprotective Effect on Immune-mediated Hepatitis and Acetaminophen-induced Liver Injury
title_sort alpha-1 anti-trypsin exerts a hepatoprotective effect on immune-mediated hepatitis and acetaminophen-induced liver injury
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328735/
https://www.ncbi.nlm.nih.gov/pubmed/30637210
http://dx.doi.org/10.14218/JCTH.2018.00030
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