{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T10:58:38Z","timestamp":1776423518814,"version":"3.51.2"},"reference-count":23,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,7,13]],"date-time":"2009-07-13T00:00:00Z","timestamp":1247443200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2009,8]]},"abstract":"<jats:p><jats:bold>Aim:\u2002<\/jats:bold> Excessive matrix metalloproteinase (MMP) activity has been implicated in the pathogenesis of acute and chronic liver injury. CTS\u20101027 is an MMP inhibitor, which has previously been studied in humans as an anti\u2010arthritic agent. Thus, our aim was to assess if CTS\u20101027 is hepato\u2010protective and anti\u2010fibrogenic during cholestatic liver injury.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> C57\/BL6 mice were subjected to bile duct ligation (BDL) for 14 days. Either CTS\u20101027 or vehicle was administered by gavage.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> BDL mice treated with CTS\u20101027 demonstrated a threefold reduction in hepatocyte apoptosis as assessed by the TUNEL assay or immunohistochemistry for caspase 3\/7\u2010positive cells as compared to vehicle\u2010treated BDL animals (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.01). A 70% reduction in bile infarcts, a histological indicator of liver injury, was also observed in CTS\u20101027\u2010treated BDL animals. These differences could not be ascribed to differences in cholestasis as serum total bilirubin concentrations were nearly identical in the BDL groups of animals. Markers for stellate cell activation (\u03b1\u2010smooth muscle actin) and hepatic fibrogenesis (collagen 1) were reduced in CTS\u20101027 versus vehicle\u2010treated BDL animals (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.05). Overall animal survival following 14 days of BDL was also improved in the group receiving the active drug (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.05).<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold> The BDL mouse, liver injury and hepatic fibrosis are attenuated by treatment with the MMP inhibitor CTS\u20101027. This drug warrants further evaluation as an anti\u2010fibrogenic drug in hepatic injury.<\/jats:p>","DOI":"10.1111\/j.1872-034x.2009.00541.x","type":"journal-article","created":{"date-parts":[[2009,7,13]],"date-time":"2009-07-13T10:44:28Z","timestamp":1247481868000},"page":"805-813","source":"Crossref","is-referenced-by-count":24,"title":["Matrix metalloproteinase inhibitor, CTS\u20101027, attenuates liver injury and fibrosis in the bile duct\u2010ligated mouse"],"prefix":"10.1111","volume":"39","author":[{"given":"Alisan","family":"Kahraman","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven F.","family":"Bronk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"Cazanave","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan 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