{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:00:19Z","timestamp":1790719219475,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2003,11,27]],"date-time":"2003-11-27T00:00:00Z","timestamp":1069891200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2003,12]]},"abstract":"<jats:p><jats:bold>Abstract: <\/jats:bold> We have previously shown that tissue\u2010type plasminogen activator (tPA) and rat plasma kallikrein (RPK) share a common, but not unique, pathway for liver clearance.<\/jats:p><jats:p><jats:bold>Aim: <\/jats:bold> To evaluate the hepatic clearance of both proteases in experimental liver fibrosis.<\/jats:p><jats:p><jats:bold>Methods: <\/jats:bold> The hepatic clearance of these proteases was studied in porcine serum\u2010induced liver fibrosis using the isolated and perfused rat liver model. To better interpret the results, we also studied four other experimental groups: the turpentine oil\u2010induced acute\u2010phase response (AP group), AP group followed by GdCl<jats:sub>3<\/jats:sub> administration (AP\/Gd group), CCl<jats:sub>4<\/jats:sub>\u2010induced cirrhosis (CCl<jats:sub>4<\/jats:sub> group) and normal group.<\/jats:p><jats:p><jats:bold>Results: <\/jats:bold> The tPA clearance decreased significantly by both fibrotic and cirrhotic rat livers whereas the RPK clearance was not altered by the fibrotic rat liver. The hepatic clearance of tPA was reduced in the AP and AP\/Gd groups; on the other hand, RPK clearance was increased in the AP group and, interestingly, this effect was neutralized by concomitant GdCl<jats:sub>3<\/jats:sub> administration.<\/jats:p><jats:p><jats:bold>Conclusions: <\/jats:bold> We observed that tPA and RPK clearances were affected differently by fibrosis as well as by different stimuli of the acute\u2010phase response, despite the fact that they share a common hepatic clearance mechanism in normal livers, and they were equally affected in cirrhosis.<\/jats:p>","DOI":"10.1111\/j.1478-3231.2003.00872.x","type":"journal-article","created":{"date-parts":[[2003,11,27]],"date-time":"2003-11-27T16:15:33Z","timestamp":1069949733000},"page":"476-483","source":"Crossref","is-referenced-by-count":19,"title":["Hepatic clearance of tissue\u2010type plasminogen activator and plasma kallikrein in experimental liver fibrosis"],"prefix":"10.1111","volume":"23","author":[{"given":"Marcia R.","family":"Nagaoka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Kouyoumdjian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Durval R.","family":"Borges","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,11,27]]},"reference":[{"key":"e_1_2_7_2_2","first-page":"3819","article-title":"Contact system","volume":"90","author":"Colman R W","year":"1997","journal-title":"a vascular biology modulator with anticoagulant, profibrinolytic, antiadhesive, and proinflammatory attributes"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(81)90443-3"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(05)80103-5"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.31885"},{"key":"e_1_2_7_6_2","first-page":"109","article-title":"Clearance of t\u2010PA, PAI\u20101, and t\u2010PA\u2013PAI\u20101 complex in an isolated perfused rat liver system","volume":"117","author":"Wing L R","year":"1991","journal-title":"J Lab Clin Med"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118105"},{"key":"e_1_2_7_8_2","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1055\/s-0038-1649930","article-title":"Characterization of the interaction of a complex of tissue\u2010type plasminogen activator and plasminogen activator inhibitor type 1 with rat liver cells","volume":"74","author":"Kuiper J","year":"1995","journal-title":"Thromb Haemost"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117023"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0162-3109(96)88182-3"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204010200"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1656000"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000046268.59922.A4"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.25480"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(98)80008-1"},{"key":"e_1_2_7_16_2","first-page":"237","article-title":"Prealbumin, prekallikrein and prothrombin in hepatoesplenic schistosomiasis","volume":"26","author":"Manoukian N","year":"1984","journal-title":"increased turnover of the clotting proteins?"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0676.1998.tb00148.x"},{"key":"e_1_2_7_18_2","first-page":"703","article-title":"Increased expression of plasminogen activator and plasminogen activator inhibitor during liver fibrogenesis of rats","volume":"31","author":"Zhang L P","year":"1999","journal-title":"role of stellate cells"},{"key":"e_1_2_7_19_2","unstructured":"International Guiding Principles for Biomedical Research Involving Animals by the Council for International Organizations of Medical Sciences (CIOMS). 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