{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:12:23Z","timestamp":1790817143348,"version":"4.1.0"},"reference-count":64,"publisher":"BMJ","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[2002,2]]},"abstract":"<jats:p>Background: The trisubstituted methylxanthine derivative pentoxifylline inhibits hepatic stellate cell proliferation and collagen synthesis in vitro. The antifibrotic effect of pentoxifylline in a suitable in vivo model of chronic liver fibrogenesis remains to be tested.<\/jats:p>\n                  <jats:p>Methods: Groups of adult rats (n=20\u201323) received oral pentoxifylline at a dose of 8 mg\/kg\/day from week 1 to week 6, and 16 mg\/kg\/day from week 1 to week 6 or week 4 to week 6 after complete bile duct occlusion. Animals who underwent sham operation that received 16 mg\/kg\/day pentoxifylline and untreated rats with bile duct occlusion alone served as controls. After six weeks, animals were sacrificed and parameters of fibrogenesis determined.<\/jats:p>\n                  <jats:p>Results: Bile duct occlusion caused portal cirrhosis with a 10-fold increased hepatic collagen content in the absence of inflammation or necrosis. This was accompanied by an 11-fold elevated serum aminoterminal procollagen III peptide (PIIINP). The drug induced a dramatic eightfold downregulation of procollagen I mRNA, and suppression of the fibrogenic factors transforming growth factor \u03b21 and connective tissue growth factor by 60\u201370%. However, profibrogenic tissue inhibitor of metalloproteinase 1 (TIMP-1) mRNA was increased twofold, resulting in only a moderate decrease in liver collagen, fibrosis score, and PIIINP.<\/jats:p>\n                  <jats:p>Conclusions: We conclude that targeting pentoxifylline to the fibrogenic cells, thereby avoiding upregulation of TIMP-1, could become a potent antifibrogenic tool in chronic liver disease.<\/jats:p>","DOI":"10.1136\/gut.50.2.241","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T06:29:07Z","timestamp":1027751347000},"page":"241-247","source":"Crossref","is-referenced-by-count":104,"title":["Pentoxifylline downregulates profibrogenic cytokines and procollagen I expression in rat secondary biliary fibrosis"],"prefix":"10.1136","volume":"50","author":[{"given":"C","family":"Raetsch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J D","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Boigk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E G","family":"Hahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E-O","family":"Riecken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Schuppan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2002,2,1]]},"reference":[{"key":"2025120523320504000_50.2.241.1","doi-asserted-by":"publisher","DOI":"10.1159\/000007494"},{"key":"2025120523320504000_50.2.241.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(96)80331-X"},{"key":"2025120523320504000_50.2.241.3","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510260316"},{"key":"2025120523320504000_50.2.241.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(00)70370-2"},{"key":"2025120523320504000_50.2.241.5","doi-asserted-by":"publisher","DOI":"10.1055\/s-2008-1040457"},{"key":"2025120523320504000_50.2.241.6","first-page":"182","volume":"52","year":"1985","journal-title":"Lab Invest"},{"key":"2025120523320504000_50.2.241.7","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(92)81290-3"},{"key":"2025120523320504000_50.2.241.8","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-198734010-00003"},{"key":"2025120523320504000_50.2.241.9","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1002\/j.1875-9114.1983.tb04533.x","volume":"3","year":"1983","journal-title":"Pharmacotherapeutica"},{"key":"2025120523320504000_50.2.241.10","first-page":"1254","volume":"35","year":"1979","journal-title":"Med Klin"},{"key":"2025120523320504000_50.2.241.11","doi-asserted-by":"publisher","DOI":"10.1007\/BF00315435"},{"key":"2025120523320504000_50.2.241.12","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1097\/00005373-199601000-00017","volume":"40","year":"1996","journal-title":"J Trauma"},{"key":"2025120523320504000_50.2.241.13","unstructured":"Chasin M, Harris DN. 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