Hepatotoxicity investigated in chemo-naive patients by proteomics

2015 Fiscal Year Final Research Report

• Project/Area Number: 25462101
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Nakano Hiroshi 聖マリアンナ医科大学, 医学部, 准教授 (10241035)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: ジヌソイド閉塞 / 抗癌剤起因性肝障害 / デフィブリド / ヒトジヌソイド内皮 / 共焦点顕微鏡 / フローサイトメトリー

Outline of Final Research Achievements

Defibrotide (DF) is a recognized as an endothelial protective agent. The aim of the study was to investigate the interaction of DF with endothelial cells (ECs). A human hepatic EC line was exposed to different DF concentrations. Using inhibitory assays and flow cytometry techniques along with confocal microscopy, we explored: DF-EC interaction, endocytic pathways, and internalization kinetics. Confocal microscopy showed interaction of DF with EC membranes followed by internalization, though DF did not reach the cell nucleus even after 24 hours. Flow cytometry revealed concentration, temperature, and time dependent uptake of DF in 2 EC models but not in other cell types. Moreover, inhibitory assays indicated that entrance of DF into ECs occurs primarily through macropinocytosis. The antiinflammatory and antioxidant properties of DF seem to be caused by the interaction of the drug with the cell membrane.

Free Research Field

外科学