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dc.contributor.author
Barreyro, Fernando Javier
dc.contributor.author
Holod, Silvia
dc.contributor.author
Finocchietto, Paola Vanesa
dc.contributor.author
Camino, Alejandra M.
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Aquino, Jorge Benjamin
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Avagnina, Alejandra
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Carreras, Maria Cecilia
dc.contributor.author
Poderoso, Juan José
dc.contributor.author
Gores, Gregory J.
dc.date.available
2017-06-22T16:30:14Z
dc.date.issued
2015-03
dc.identifier.citation
Barreyro, Fernando Javier; Holod, Silvia; Finocchietto, Paola Vanesa; Camino, Alejandra M.; Aquino, Jorge Benjamin; et al.; The Pan-Caspase Inhibitor Emricasan (IDN-6556) decreases liver injury and fibrosis in a murine model of non-alcoholic steatohepatitis; Wiley; Liver International; 35; 3; 3-2015; 953-966
dc.identifier.issn
1478-3223
dc.identifier.uri
http://hdl.handle.net/11336/18641
dc.description.abstract
BACKGROUND & AIMS: Hepatocyte apoptosis, the hallmark of non-alcoholic steatohepatitis (NASH) contributes to liver injury and fibrosis. Although, both the intrinsic and extrinsic apoptotic pathways are involved in the pathogenesis of NASH, the final common step of apoptosis is executed by a family of cysteine-proteases termed caspases. Thus, our aim was to ascertain if administration of Emricasan, a pan-caspase inhibitor, ameliorates liver injury and fibrosis in a murine model of NASH. METHODS: C57/BL6J-mice were fed regular chow or high fat diet (HFD) for 20 weeks. All mice were treated with vehicle or Emricasan. RESULTS: Mice fed a HFD diet demonstrate a five-fold increase in hepatocyte apoptosis by the TUNEL assay and a 1.5-fold and 1.3-fold increase in caspase-3 and-8 activities respectively; this increase in apoptosis was substantially attenuated in mice fed a HFD treated with Emricasan (HFD-Em). Likewise, liver injury and inflammation were reduced in mice fed HFD-Em as compare to HFD by measuring serum aspartate aminotransferase and alanine aminotransferase levels, NAS histological score and IL 1-β, TNF-α, monocyte chemoattractant protein (MCP-1) and C-X-C chemokine ligand-2 (CXCL2) quantitative reverse-transcription polymerase chain reaction (qPCR). These differences could not be attributed to differences in hepatic steatosis as liver triglycerides content were similar in both HFD groups. Hepatic fibrosis was reduced by Emricasan in HFD animals by decreasing αSMA (a marker for hepatic stellate cell activation), fibrosis score, Sirius red staining, hydroxyproline liver content and profibrogenic cytokines by qPCR. CONCLUSION: In conclusion, these data demonstrate that in a murine model of NASH, liver injury and fibrosis are suppressed by inhibiting hepatocytes apoptosis and suggests that Emricasan may be an attractive antifibrotic therapy in NASH.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Wiley
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc/2.5/ar/
dc.subject
Apoptosis
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Caspase Inhibitor
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Emricasan
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Fibrosis
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Non-Alcoholic Fatty Liver Disease
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Bioquímica y Biología Molecular
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
The Pan-Caspase Inhibitor Emricasan (IDN-6556) decreases liver injury and fibrosis in a murine model of non-alcoholic steatohepatitis
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-06-21T17:39:18Z
dc.identifier.eissn
1478-3231
dc.journal.volume
35
dc.journal.number
3
dc.journal.pagination
953-966
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Hoboken
dc.description.fil
Fil: Barreyro, Fernando Javier. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales. Departamento de Microbiología; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Metabolismo del Oxígeno; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Holod, Silvia. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Metabolismo del Oxígeno; Argentina
dc.description.fil
Fil: Finocchietto, Paola Vanesa. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Metabolismo del Oxígeno; Argentina
dc.description.fil
Fil: Camino, Alejandra M.. DIM Clínica Privada; Argentina
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Fil: Aquino, Jorge Benjamin. Universidad Austral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Avagnina, Alejandra. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
dc.description.fil
Fil: Carreras, Maria Cecilia. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Metabolismo del Oxígeno; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Poderoso, Juan José. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Metabolismo del Oxígeno; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Gores, Gregory J.. Mayo Clinic College of Medicine; Estados Unidos
dc.journal.title
Liver International
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/liv.12570/abstract
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1111/liv.12570


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