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The lectin-like domain of thrombomodulin is a drug candidate for both prophylaxis and treatment of liver ischemia and reperfusion injury in mice.
Kawasoe, Junya; Uchida, Yoichiro; Miyauchi, Tomoyuki; Kadono, Kentaro; Hirao, Hirofumi; Saga, Kenichi; Watanabe, Takeshi; Ueda, Shugo; Terajima, Hiroaki; Uemoto, Shinji.
Afiliación
  • Kawasoe J; Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Uchida Y; Department of Gastroenterological Surgery and Oncology, The Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan.
  • Miyauchi T; Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Kadono K; Department of Gastroenterological Surgery and Oncology, The Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan.
  • Hirao H; Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Saga K; Department of Gastroenterological Surgery and Oncology, The Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan.
  • Watanabe T; Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Ueda S; Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Terajima H; Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Uemoto S; Department of Gastroenterological Surgery and Oncology, The Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan.
Am J Transplant ; 21(2): 540-551, 2021 02.
Article en En | MEDLINE | ID: mdl-32805077
Ischemia and reperfusion injury (IRI) can occur in any tissue or organ. With respect to liver transplantation, the liver grafts from donors by definition experience transient ischemia and subsequent blood reflow. IRI is a problem not only in organ transplantation but also in cases of thrombosis or circulatory disorders such as mesenteric ischemia, myocardial, or cerebral infarction. We have reported that recombinant human soluble thrombomodulin (rTM), which is currently used in Japan to treat disseminated intravascular coagulation (DIC), has a protective effect and suppresses liver IRI in mice. However, rTM may not be fully safe to use in humans because of its inherent anticoagulant activity. In the present study, we used a mouse liver IRI model to explore the possibility that the isolated lectin-like domain of rTM (rTMD1), which has no anticoagulant activity, could be effective as a therapeutic modality for IRI. Our results indicated that rTMD1 could suppress ischemia and reperfusion-induced liver damage in a dose-dependent manner without concern of associated hemorrhage. Surprisingly, rTMD1 suppressed the liver damage even after IR insult had occurred. Taken together, we conclude that rTMD1 may be a candidate drug for prevention of and therapy for human liver IRI without the possible risk of hemorrhage.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Preparaciones Farmacéuticas / Daño por Reperfusión Límite: Animals País/Región como asunto: Asia Idioma: En Revista: Am J Transplant Asunto de la revista: TRANSPLANTE Año: 2021 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Preparaciones Farmacéuticas / Daño por Reperfusión Límite: Animals País/Región como asunto: Asia Idioma: En Revista: Am J Transplant Asunto de la revista: TRANSPLANTE Año: 2021 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos