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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.
dc.contributor.author Aquino, Jorge Benjamin
dc.contributor.author Avagnina, Alejandra
dc.contributor.author 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
dc.subject Caspase inhibitor
dc.subject Emricasan
dc.subject Fibrosis
dc.subject Non-alcoholic fatty liver disease
dc.subject.classification Bioquímica y Biología Molecular
dc.subject.classification Medicina Básica
dc.subject.classification 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
dc.description.fil 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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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial 2.5 Unported (CC BY-NC 2.5)