{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:02:59Z","timestamp":1792011779629,"version":"4.4.0"},"reference-count":70,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,6,6]],"date-time":"2014-06-06T00:00:00Z","timestamp":1402012800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Agencia Nacional para la Promocion Cientifica y Tecnologica","award":["PICT-O UNAM-2011"],"award-info":[{"award-number":["PICT-O UNAM-2011"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Hepatocyte apoptosis, the hallmark of non\u2010alcoholic steatohepatitis (<jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>) contributes to liver injury and fibrosis. Although, both the intrinsic and extrinsic apoptotic pathways are involved in the pathogenesis of<jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>, the final common step of apoptosis is executed by a family of cysteine\u2010proteases termed caspases. Thus, our aim was to ascertain if administration of Emricasan, a pan\u2010caspase inhibitor, ameliorates liver injury and fibrosis in a murine model of<jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>C57\/<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>6J\u2010mice were fed regular chow or high fat diet (<jats:styled-content style=\"fixed-case\">HFD<\/jats:styled-content>) for 20\u00a0weeks. All mice were treated with vehicle or Emricasan.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mice fed a HFD diet demonstrate a five\u2010fold increase in hepatocyte apoptosis by the TUNEL assay and a 1.5\u2010fold and 1.3\u2010fold increase in caspase\u20103 and\u20108 activities respectively; this increase in apoptosis was substantially attenuated in mice fed a HFD treated with Emricasan (HFD\u2010Em). Likewise, liver injury and inflammation were reduced in mice fed HFD\u2010Em as compare to HFD by measuring serum aspartate aminotransferase and alanine aminotransferase levels, NAS histological score and IL 1\u2010\u03b2, TNF\u2010\u03b1, monocyte chemoattractant protein (MCP\u20101) and C\u2010X\u2010C chemokine ligand\u20102 (CXCL2) quantitative reverse\u2010transcription 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 \u03b1SMA (a marker for hepatic stellate cell activation), fibrosis score, Sirius red staining, hydroxyproline liver content and profibrogenic cytokines by qPCR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In conclusion, these data demonstrate that in a murine model of<jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>, liver injury and fibrosis are suppressed by inhibiting hepatocytes apoptosis and suggests that Emricasan may be an attractive antifibrotic therapy in<jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12570","type":"journal-article","created":{"date-parts":[[2014,4,22]],"date-time":"2014-04-22T07:41:33Z","timestamp":1398152493000},"page":"953-966","source":"Crossref","is-referenced-by-count":283,"title":["The pan\u2010caspase inhibitor Emricasan (<scp>IDN<\/scp>\u20106556) decreases liver injury and fibrosis in a murine model of non\u2010alcoholic steatohepatitis"],"prefix":"10.1111","volume":"35","author":[{"given":"Fernando J.","family":"Barreyro","sequence":"first","affiliation":[{"name":"Laboratory of Microbiology Faculty of Chemical and Natural Sciences National University of Misiones CONICET (Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas) Posadas Argentina"},{"name":"Laboratory of Oxygen Metabolism University Hospital University of Buenos Aires Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Holod","sequence":"additional","affiliation":[{"name":"Laboratory of Oxygen Metabolism University Hospital University of Buenos Aires Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola V.","family":"Finocchietto","sequence":"additional","affiliation":[{"name":"Laboratory of Oxygen Metabolism University Hospital University of Buenos Aires Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra M.","family":"Camino","sequence":"additional","affiliation":[{"name":"Laboratorio de Morfometr\u00eda DIM Clinica Privada Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge B.","family":"Aquino","sequence":"additional","affiliation":[{"name":"Liver Unit School of Medicine Austral University Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Avagnina","sequence":"additional","affiliation":[{"name":"Department of Pathology University Hospital University of Buenos Aires Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda C.","family":"Carreras","sequence":"additional","affiliation":[{"name":"Laboratory of Oxygen Metabolism University Hospital University of Buenos Aires Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan J.","family":"Poderoso","sequence":"additional","affiliation":[{"name":"Laboratory of Oxygen Metabolism University Hospital University of Buenos Aires Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory J.","family":"Gores","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Mayo Clinic College of Medicine Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,6,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.04.008"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra011775"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.04.001"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2011.04724.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(03)00907-7"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21223"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(03)00460-4"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2006.118059"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21846"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2009.05785.x"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M510660200"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.022491"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20283"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-0570"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.297"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.05.004"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2004.053850"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/35048069"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50472"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.LAB.0000069036.63405.5C"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.SC0070207"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.103.060129"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2001.tb02300.x"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23167"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.03.016"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm050307e"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21664"},{"key":"e_1_2_7_29_1","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1111\/j.1365-2036.2010.04264.x","article-title":"Clinical trial: the efficacy and safety of oral PF\u201003491390, a pancaspase inhibitor \u2013 a randomized placebo\u2010controlled study in patients with chronic hepatitis C","volume":"31","author":"Shiffman ML","year":"2007","journal-title":"Aliment Pharmacol Ther"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2008.05.017"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:DDAS.0000043367.69470.b7"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00280883"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20255"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(79)90738-3"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00377.2007"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22136"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.1228"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20701"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M409752200"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1542-3565(04)00616-0"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23535"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1080\/00365520802588133"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2006.07.006"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M900022-JLR200"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.90272.2008"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22363"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23797"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21874"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2004.04.017"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-006-9148-7"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.280420"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601460"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00091.2010"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.04.027"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M704391200"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24747"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02982714"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOL.0b013e3282ff5e55"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2012.45"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24341"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1159\/000318741"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23046"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0056100"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-4828com"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30542"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.03.003"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c120020"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23479"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)61101-7"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24516"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09075"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fliv.12570","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fliv.12570","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.12570","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,26]],"date-time":"2024-05-26T03:26:37Z","timestamp":1716693997000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.12570"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,6,6]]},"references-count":70,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,3]]}},"alternative-id":["10.1111\/liv.12570"],"URL":"https:\/\/doi.org\/10.1111\/liv.12570","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,6,6]]}}}