{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:07:00Z","timestamp":1788869220475,"version":"build-2803163510"},"reference-count":61,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2002,10,18]],"date-time":"2002-10-18T00:00:00Z","timestamp":1034899200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006589","name":"Ministry of Science and Technology, Croatia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006589","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2002,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Liver cirrhosis (LC) is a chronic disease with high mortality rate. In the United States and Western world as well as Asian countries, LC is the major leading cause of death by disease. Yet, no effective therapeutic agent is available for LC treatment. Laboratory cirrhotic rats produced by dimethylnitrosamine administrations simulate the clinical features of human LC such as mortality, ascites, hepatic parenchymal cell destruction, and formation of connective tissue and nodular regeneration, providing a preclinical model to evaluate therapeutic efficacy of drugs and the underlying mechanisms. Oltipraz [5\u2010(2\u2010pyrazinyl)\u20104\u2010methyl\u20101,2\u2010dithiol\u20103\u2010thione] has been used clinically and is of little toxicity. Comprehensive mechanistic and phase IIa clinical studies supported the notion that oltipraz exerts chemopreventive effects against chemical carcinogenesis. We report here that oltipraz within the clinical dose range regenerates cirrhotic liver in the established LC rats as a result of reduction of the intensities of cirrhotic nodules, elimination of accumulated extracellular matrix, and inactivation of stellate cells, thereby improving survival rate. We also reveal that activation of CCAAT\/enhancer binding protein by oltipraz inhibits transforming growth factor \u03b21 gene expression in stellate cells, which provides a molecular target for pharmacological treatment of LC. Oltipraz is the first therapeutic agent that regenerates cirrhotic liver.<\/jats:p>","DOI":"10.1096\/fj.02-0406fje","type":"journal-article","created":{"date-parts":[[2002,12,5]],"date-time":"2002-12-05T12:43:29Z","timestamp":1039092209000},"page":"1988-1990","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":76,"title":["Oltipraz regenerates cirrhotic liver through CCAAT\/enhancer binding protein\u2010mediated stellate cell inactivation"],"prefix":"10.1096","volume":"16","author":[{"given":"Keon","family":"Wook Kang","sequence":"first","affiliation":[{"name":"National Research Laboratory Seoul National University  Seoul Korea"},{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences Seoul National University  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon","family":"Gyoon Kim","sequence":"additional","affiliation":[{"name":"National Research Laboratory Seoul National University  Seoul Korea"},{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences Seoul National University  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Kyong Cho","sequence":"additional","affiliation":[{"name":"National Research Laboratory Seoul National University  Seoul Korea"},{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences Seoul National University  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo","family":"Kyung Bae","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences Seoul National University  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Choon","family":"Won Kim","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology Hanyang University Medical School  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myung","family":"Gull Lee","sequence":"additional","affiliation":[{"name":"National Research Laboratory Seoul National University  Seoul Korea"},{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences Seoul National University  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang","family":"Geon Kim","sequence":"additional","affiliation":[{"name":"National Research Laboratory Seoul National University  Seoul Korea"},{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences Seoul National University  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,10,18]]},"reference":[{"key":"e_1_2_6_2_1","article-title":"Liver cirrhosis mortality in the United States, 1970\u20131993","author":"DeBakey S. 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