{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T03:39:56Z","timestamp":1790048396041,"version":"4.0.1"},"reference-count":36,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2012,1,24]],"date-time":"2012-01-24T00:00:00Z","timestamp":1327363200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2012,1,24]],"date-time":"2012-01-24T00:00:00Z","timestamp":1327363200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Alcoholism Clin &amp; Exp Res"],"published-print":{"date-parts":[[2012,7]]},"abstract":"\n Background:<\/jats:title>\n \n Correlative evidence indicates that apoptosis is associated with the progression of alcoholic liver disease. If apoptosis contributes to ethanol (\n EtOH<\/jats:styled-content>\n )\u2010induced steatohepatitis and\/or fibrosis, then mice deficient in\n B<\/jats:styled-content>\n id, a key pro\u2010apoptotic\n B<\/jats:styled-content>\n cl\u20102 family member, or mice treated with a pan\u2010caspase inhibitor (\n VX<\/jats:styled-content>\n 166) should be resistant to\n EtOH<\/jats:styled-content>\n \u2010induced liver injury.\n <\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n \n This hypothesis was tested in mice using a model of chronic, heavy\n EtOH<\/jats:styled-content>\n \u2010induced liver injury, as well as in a model in which moderate\n EtOH<\/jats:styled-content>\n feeding accelerated the appearance of early markers of hepatic fibrosis in response to acute carbon tetrachloride (CCl\n 4<\/jats:sub>\n ) exposure.\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n Chronic\n EtOH<\/jats:styled-content>\n feeding to mice increased\n TUNEL<\/jats:styled-content>\n \u2010 and cytokeratin\u201018\u2010positive cells in the liver, as well as the expression of receptor\u2010interacting protein kinase 3 (\n RIP<\/jats:styled-content>\n 3), a marker of necroptosis. In this model,\n B<\/jats:styled-content>\n id\u2212\/\u2212 mice or wild\u2010type mice treated with\n VX<\/jats:styled-content>\n 166 were protected from\n EtOH<\/jats:styled-content>\n \u2010induced apoptosis, but not\n EtOH<\/jats:styled-content>\n \u2010induced\n RIP<\/jats:styled-content>\n 3 expression. Bid deficiency or inhibition of caspase activity did not protect mice from\n EtOH<\/jats:styled-content>\n \u2010induced increases in plasma alanine and aspartate amino transferase activity, steatosis, or\n mRNA<\/jats:styled-content>\n expression of some inflammatory cytokines. Moderate\n EtOH<\/jats:styled-content>\n feeding to mice enhanced the response of mice to acute CCl\n 4<\/jats:sub>\n exposure, resulting in increased expression of \u03b1\u2010smooth muscle actin and accumulation of extracellular matrix protein.\n VX<\/jats:styled-content>\n 166\u2010treatment attenuated\n EtOH<\/jats:styled-content>\n \u2010mediated acceleration of these early indicators of CCl\n 4<\/jats:sub>\n \u2010induced hepatic fibrosis, decreasing the expression of \u03b1\u2010smooth muscle actin, and the accumulation of extracellular matrix protein.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n \n EtOH\u2010induced apoptosis of hepatocytes was mediated by\n B<\/jats:styled-content>\n id. Apoptosis played a critical role in the accelerating the appearance of early markers of CCl\n 4<\/jats:sub>\n \u2010induced fibrosis by moderate\n EtOH<\/jats:styled-content>\n but did not contribute to\n EtOH<\/jats:styled-content>\n \u2010induced hepatocyte injury, steatosis, or expression of\n mRNA<\/jats:styled-content>\n for some inflammatory cytokines.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/j.1530-0277.2011.01720.x","type":"journal-article","created":{"date-parts":[[2012,1,24]],"date-time":"2012-01-24T13:59:22Z","timestamp":1327413562000},"page":"1139-1147","source":"Crossref","is-referenced-by-count":75,"title":["Inhibition of Apoptosis Protects Mice from Ethanol\u2010Mediated Acceleration of Early Markers of\n CC<\/scp>\n l\n 4<\/sub>\n \u2010Induced Fibrosis but not Steatosis or Inflammation"],"prefix":"10.1111","volume":"36","author":[{"given":"Sanjoy","family":"Roychowdhury","sequence":"first","affiliation":[{"name":"Center for Liver Disease Research Departments of Pathobiology Case Western Reserve University Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dian J.","family":"Chiang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Case Western Reserve University Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Palash","family":"Mandal","sequence":"additional","affiliation":[{"name":"Center for Liver Disease Research Departments of Pathobiology Case Western Reserve University Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan R.","family":"McMullen","sequence":"additional","affiliation":[{"name":"Center for Liver Disease Research Departments of Pathobiology Case Western Reserve University Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuli","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology Cleveland Clinic Case Western Reserve University Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica I.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Center for Liver Disease Research Departments of Pathobiology Case Western Reserve University Cleveland Ohio"},{"name":"Department of Nutrition Case Western Reserve University Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Pollard","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals (Europe) Abingdon UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariel E.","family":"Feldstein","sequence":"additional","affiliation":[{"name":"Department of Cell Biology Case Western Reserve University Cleveland Ohio"},{"name":"Department of Pediatric Endocrinology Case Western Reserve University Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura E.","family":"Nagy","sequence":"additional","affiliation":[{"name":"Center for Liver Disease Research Departments of Pathobiology Case Western Reserve University Cleveland Ohio"},{"name":"Department of Gastroenterology Case Western Reserve University Cleveland Ohio"},{"name":"Department of Nutrition Case Western Reserve University Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,1,24]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.03.016"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2006.01595.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(88)80024-2"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.103.060129"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.04.041"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2001.tb02300.x"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20310"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/01926230701320337"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-1007150"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2004.053850"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.0350964"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.09.034"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21062"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002060"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2009.05.010"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2004.056929"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.2131\/jts.32.453"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/153537020322800803"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.090304"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.04.017"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.091186"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00325.2007"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.22314"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22776"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2009.07.015"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v16.i11.1321"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070247"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2970"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23167"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1006\/taap.1998.8547"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s001090000099"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cr.7290045"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1172308"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)61699-9"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(00)00047-7"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22973"}],"container-title":["Alcoholism: 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