Alpha-1 Anti-trypsin Exerts a Hepatoprotective Effect on Immune-mediated Hepatitis and Acetaminophen-induced Liver Injury
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 determi...
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| Published in | Journal of clinical and translational hepatology Vol. 6; no. 4; pp. 345 - 349 |
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| Main Authors | , , |
| Format | Journal Article |
| Language | English |
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China
Gastroenterology and Liver Units, Department of Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, Israel
28.12.2018
XIA & HE Publishing Inc |
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| Abstract | 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.
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.
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.
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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| AbstractList | 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.
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.
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.
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. 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 antiprotease 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:AATwas 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 AATalleviated concanavalin A-induced immunemediated 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. 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. |
| Author | Ya'acov, Ami Ben Shabat, Yehudit Ilan, Yaron |
| AuthorAffiliation | Gastroenterology and Liver Units, Department of Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, Israel |
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| CitedBy_id | crossref_primary_10_11603_mcch_2410_681X_2019_v_i4_10845 crossref_primary_10_1016_j_cellimm_2020_104157 |
| Cites_doi | 10.1073/pnas.0807627105 10.1007/s00296-013-2745-9 10.1007/s00005-012-0162-5 10.1371/journal.pone.0033254 10.1586/ers.11.20 10.1016/j.jhep.2013.03.033 10.1002/path.1869 10.3389/fimmu.2014.00177 10.1016/j.jhep.2015.04.016 10.1007/s11894-999-0086-3 10.1111/j.1365-2249.1992.tb06484.x 10.2174/156652412801318755 10.1111/j.1464-5491.2008.02584.x 10.1097/MCG.0b013e31827873dc 10.1093/rheumatology/ker123 10.2174/0929867321666140916122628 10.4161/auto.4906 10.2119/molmed.2011.00145 10.1038/nrgastro.2013.149 10.1016/j.cld.2007.06.006 10.1002/hep.27024 10.1111/imm.12149 10.1007/s10875-015-0160-6 10.1189/jlb.72.2.262 10.4049/jimmunol.1101340 10.1097/ACI.0000000000000070 10.3389/fimmu.2013.00320 10.1007/s11892-009-0018-5 10.1111/cei.12476 10.1073/pnas.1117665109 10.1371/journal.pone.0177279 10.1007/s11239-007-0088-7 10.3748/wjg.v21.i24.7443 10.1152/ajpgi.00105.2005 10.1093/infdis/jiu620 |
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| Keywords | Alpha-1 anti-trypsin Drug-induced liver injury Chronic liver disease Acetaminophen Druginduced liver injury |
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| Title | Alpha-1 Anti-trypsin Exerts a Hepatoprotective Effect on Immune-mediated Hepatitis and Acetaminophen-induced Liver Injury |
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