The effects of tesmilifene, a chemopotentiating agent, on brain endothelial cells

Abstract

Event Abstract Back to Event The effects of tesmilifene, a chemopotentiating agent, on brain endothelial cells Fruzsina Walter1*, Szilvia Veszelka1, Csongor Ábrahám1 and Mária Deli1 1 Hungarian Academy of Sciences, Group of Molecular Neurobiology, Institute of Biophysics, Biological Research Center, Hungary Tesmilifene, a tamoxifen-related compound, has chemopotentiating and cytoprotective properties in experimental and clinical studies. Treatment with tesmilifene caused temporary central nervous system side-effects in patients indicating the opening of the blood-brain barrier. Previous studies from our laboratory have shown that tesmilifene increases the permeability of the blood-brain barrier in rats. The aim of the present study was to test the direct effects of tesmilifene on blood-brain barrier functions using a cell culture-based model. Primary rat brain endothelial and glial cells were co-cultured using Transwell inserts and treated with tesmilifene (1-400 µM). Barrier integrity was measured by transendothelial electrical resistance and permeability for markers fluorescein and albumin. Activity of P-glycoprotein and multidrug resistance protein-1 was tested in the presence of inhibitors and tesmilifene. DAF-FM diacetate was used as a fluorescent indicator of nitric oxide release. MTT and lactate dehydrogenase assays were used as toxicity tests. Short-term tesmilifene treatment decreased the transendothelial electrical resistance of endothelial monolayers, and increased the permeability for albumin. Tesmilifene did not change the functions of P-glycoprotein, but significantly decreased the activity of the multidrug resistance associated protein-1 and the production of vasoactive mediator nitric oxide. Long-term tesmilifene treatment dose-dependently reduced the viability of brain endothelial cells. Tesmilifene affected several blood-brain barrier functions, decreased the barrier integrity, inhibited the activity of the MRP-1 efflux pump, and caused toxic effects in concentrations exceeding the therapeutical level in brain endothelial cells. Our data indicate that tesmilifene increases the permeability of the blood-brain barrier by directly acting on brain endothelial cells and could be exploited to promote drug transport to brain. Conference: IBRO International Workshop 2010, Pécs, Hungary, 21 Jan - 23 Jan, 2010. Presentation Type: Poster Presentation Topic: Homeostatic and neuroendocrine systems Citation: Walter F, Veszelka S, Ábrahám C and Deli M (2010). The effects of tesmilifene, a chemopotentiating agent, on brain endothelial cells. Front. Neurosci. Conference Abstract: IBRO International Workshop 2010. doi: 10.3389/conf.fnins.2010.10.00140 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 29 Apr 2010; Published Online: 29 Apr 2010. * Correspondence: Fruzsina Walter, Hungarian Academy of Sciences, Group of Molecular Neurobiology, Institute of Biophysics, Biological Research Center, Szeged, Hungary, walter@brc.hu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Fruzsina Walter Szilvia Veszelka Csongor Ábrahám Mária Deli Google Fruzsina Walter Szilvia Veszelka Csongor Ábrahám Mária Deli Google Scholar Fruzsina Walter Szilvia Veszelka Csongor Ábrahám Mária Deli PubMed Fruzsina Walter Szilvia Veszelka Csongor Ábrahám Mária Deli Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.