{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T09:40:33Z","timestamp":1773740433236,"version":"3.50.1"},"reference-count":49,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,1,26]],"date-time":"2018-01-26T00:00:00Z","timestamp":1516924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aim<\/jats:title><jats:p>Sinusoidal obstruction syndrome (SOS) is a serious drug\u2010induced liver injury. However, the pathophysiology of the disease remains unclear. This study investigated the effects of cilostazol (CZ), a phosphodiesterase III inhibitor, in a monocrotaline (MCT)\u2010induced rat model of SOS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male Wistar rats were administrated MCT to induce SOS. Rats were divided into control, MCT, and MCT\u00a0+\u00a0CZ groups. In the MCT\u00a0+\u00a0CZ group, CZ was administered at 48\u00a0h, 24\u00a0h, and 30\u00a0min prior to and 8\u00a0h and 24\u00a0h after MCT administration. The MCT group was treated with water instead of CZ. At 48\u00a0h after MCT administration, blood and liver samples were collected to assess biochemistry and liver histology. Expression of rat endothelial cell antigen, CD34, CD41, P\u2010selectin, and caspase\u20103 in the liver were analyzed. Plasminogen activator inhibitor\u20101 (PAI\u20101) in hepatocytes was analyzed using western blotting and polymerase chain reaction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the MCT group, macroscopic findings showed a dark\u2010red liver surface. Histological findings showed sinusoidal dilatation, coagulative necrosis of hepatocytes, and endothelial damage of the central vein. These changes were attenuated in the MCT\u00a0+\u00a0CZ group. Elevated serum transaminase and decreased platelet counts were observed in the MCT\u00a0+\u00a0CZ group compared with those in the MCT group. Treatment with CZ reduced MCT\u2010induced damage to the liver sinusoidal endothelial cells, inhibited extravasated platelet aggregation, and suppressed hepatocyte apoptosis around the central vein. CZ attenuated hepatic PAI\u20101 protein and mRNA levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Cilostazol attenuated MCT\u2010induced SOS by preventing damage to liver sinusoidal endothelial cells and extravasated platelet aggregation. Hepatic PAI\u20101 levels were suppressed with CZ treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.14004","type":"journal-article","created":{"date-parts":[[2017,9,28]],"date-time":"2017-09-28T16:02:33Z","timestamp":1506614553000},"page":"950-957","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Phosphodiesterase III inhibitor attenuates rat sinusoidal obstruction syndrome through inhibition of platelet aggregation in Disse's space"],"prefix":"10.1111","volume":"33","author":[{"given":"Takashi","family":"Miyata","sequence":"first","affiliation":[{"name":"Department of Gastroenterological Surgery, Division of Cancer Medicine Kanazawa University  Kanazawa Ishikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidehiro","family":"Tajima","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Division of Cancer Medicine Kanazawa University  Kanazawa Ishikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miki","family":"Hirata","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Division of Cancer Medicine Kanazawa University  Kanazawa Ishikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shin\u2010ichi","family":"Nakanuma","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Division of Cancer Medicine Kanazawa University  Kanazawa Ishikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isamu","family":"Makino","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Division of Cancer Medicine Kanazawa University  Kanazawa Ishikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hironori","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Division of Cancer Medicine Kanazawa University  Kanazawa Ishikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsunobu","family":"Oyama","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Division of Cancer Medicine Kanazawa University  Kanazawa Ishikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoharu","family":"Miyashita","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Division of Cancer Medicine Kanazawa University  Kanazawa Ishikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Takamura","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Division of Cancer Medicine Kanazawa University  Kanazawa Ishikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Itasu","family":"Ninomiya","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Division of Cancer Medicine Kanazawa University  Kanazawa Ishikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sachio","family":"Fushida","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Division of Cancer Medicine Kanazawa University  Kanazawa Ishikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shoichi","family":"Iseki","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Division of Cancer Medicine Kanazawa University  Kanazawa Ishikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shin\u2010ichi","family":"Harada","sequence":"additional","affiliation":[{"name":"Center for Biomedical Research, Graduate School of Medicine Kanazawa University  Kanazawa Ishikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohiko","family":"Wakayama","sequence":"additional","affiliation":[{"name":"Department of Histology, Faculty of Life Sciences Kumamoto University  Kumamoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuo","family":"Ohta","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Division of Cancer Medicine Kanazawa University  Kanazawa Ishikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,1,26]]},"reference":[{"key":"e_1_2_5_2_1","first-page":"285","article-title":"Veno\u2010occlusive disease of liver with nonportal type of cirrhosis, occurring in Jamaica","volume":"57","author":"Bras G","year":"1954","journal-title":"A.M.A. Arch. 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