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The new cardioprotector Monohydroxyethylrutoside protects against doxorubicin-induced inflammatory effects in vitro
Besides its cardiotoxic effect, doxorubicin also elicits inflammatory effects in vivo. 7-Monohydroxyethylrutoside (monoHER) has recently been used as a protector against doxorubicin-induced cardiotoxicity in vivo. It is not known yet whether monoHER can also protect against doxorubicin-induced infla...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2003
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2394271/ https://www.ncbi.nlm.nih.gov/pubmed/12865930 http://dx.doi.org/10.1038/sj.bjc.6601022 |
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author | Abou El Hassan, M A I Verheul, H M W Jorna, A S Schalkwijk, C van Bezu, J van der Vijgh, W J F Bast, A |
author_facet | Abou El Hassan, M A I Verheul, H M W Jorna, A S Schalkwijk, C van Bezu, J van der Vijgh, W J F Bast, A |
author_sort | Abou El Hassan, M A I |
collection | PubMed |
description | Besides its cardiotoxic effect, doxorubicin also elicits inflammatory effects in vivo. 7-Monohydroxyethylrutoside (monoHER) has recently been used as a protector against doxorubicin-induced cardiotoxicity in vivo. It is not known yet whether monoHER can also protect against doxorubicin-induced inflammatory effects. The aim of the present study was (1) to illustrate the inflammatory effects of doxorubicin in vitro and (2) to evaluate a possibly protective effect of monoHER. In order to demonstrate the inflammatory effects of doxorubicin and the possible protection of monoHER, proliferating human umbilical cord vascular endothelial cells (HUVECs) were incubated with different concentrations of doxorubicin ranging from 12.5 to 600 nM with(out) 200 μM monoHER. Resting (confluent) HUVECs were incubated with (0.5–25 μM) doxorubicin with(out) monoHER (0.2–1.2 mM) and the viability of endothelial cells and their propensity to adhere to neutrophils were measured 24 h after treatment. The localisation of adhered neutrophils was determined with immunofluorescence microscopy. To further characterise the mechanism of doxorubicin-induced neutrophil adhesion, the expression of the HUVECs surface adhesion molecules was determined after doxorubicin treatment. Doxorubicin decreased the viability and proliferation capacity of HUVECs in a concentration-dependent manner. The proliferating HUVECs were much more sensitive to doxorubicin (IC(50)=60.0±20.8 nM) than resting cells (LC(50)=4.0±0.3 μM). Doxorubicin also increased the adhesion of neutrophils reaching a plateau value at a doxorubicin concentration of ⩾0.4μM (P=0.0113). The induced neutrophil adhesion was accompanied by overexpression of VCAM and E-selectin but not ICAM. Although monoHER did not reverse the effect of doxorubicin on the proliferation of endothelial cells, it significantly protected resting HUVECs against the cytotoxic effect of doxorubicin (⩽25 μM, P<0.0015). In addition, monoHER completely protected against the stimulatory effect of doxorubicin on neutrophil adhesion, and inhibited the doxorubin-induced expression of VCAM and E-selectin on the surface of treated HUVECs. This study illustrates that monoHER, which protects against doxorubicin's cardiotoxic effect, can also protect against doxorubicin-induced inflammatory effects. These data prompt further investigation about the possible link between doxorubicin-induced inflammatory effects and its cardiotoxicity in vivo. |
format | Text |
id | pubmed-2394271 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2003 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-23942712009-09-10 The new cardioprotector Monohydroxyethylrutoside protects against doxorubicin-induced inflammatory effects in vitro Abou El Hassan, M A I Verheul, H M W Jorna, A S Schalkwijk, C van Bezu, J van der Vijgh, W J F Bast, A Br J Cancer Experimental Therapeutics Besides its cardiotoxic effect, doxorubicin also elicits inflammatory effects in vivo. 7-Monohydroxyethylrutoside (monoHER) has recently been used as a protector against doxorubicin-induced cardiotoxicity in vivo. It is not known yet whether monoHER can also protect against doxorubicin-induced inflammatory effects. The aim of the present study was (1) to illustrate the inflammatory effects of doxorubicin in vitro and (2) to evaluate a possibly protective effect of monoHER. In order to demonstrate the inflammatory effects of doxorubicin and the possible protection of monoHER, proliferating human umbilical cord vascular endothelial cells (HUVECs) were incubated with different concentrations of doxorubicin ranging from 12.5 to 600 nM with(out) 200 μM monoHER. Resting (confluent) HUVECs were incubated with (0.5–25 μM) doxorubicin with(out) monoHER (0.2–1.2 mM) and the viability of endothelial cells and their propensity to adhere to neutrophils were measured 24 h after treatment. The localisation of adhered neutrophils was determined with immunofluorescence microscopy. To further characterise the mechanism of doxorubicin-induced neutrophil adhesion, the expression of the HUVECs surface adhesion molecules was determined after doxorubicin treatment. Doxorubicin decreased the viability and proliferation capacity of HUVECs in a concentration-dependent manner. The proliferating HUVECs were much more sensitive to doxorubicin (IC(50)=60.0±20.8 nM) than resting cells (LC(50)=4.0±0.3 μM). Doxorubicin also increased the adhesion of neutrophils reaching a plateau value at a doxorubicin concentration of ⩾0.4μM (P=0.0113). The induced neutrophil adhesion was accompanied by overexpression of VCAM and E-selectin but not ICAM. Although monoHER did not reverse the effect of doxorubicin on the proliferation of endothelial cells, it significantly protected resting HUVECs against the cytotoxic effect of doxorubicin (⩽25 μM, P<0.0015). In addition, monoHER completely protected against the stimulatory effect of doxorubicin on neutrophil adhesion, and inhibited the doxorubin-induced expression of VCAM and E-selectin on the surface of treated HUVECs. This study illustrates that monoHER, which protects against doxorubicin's cardiotoxic effect, can also protect against doxorubicin-induced inflammatory effects. These data prompt further investigation about the possible link between doxorubicin-induced inflammatory effects and its cardiotoxicity in vivo. Nature Publishing Group 2003-07-21 2003-07-15 /pmc/articles/PMC2394271/ /pubmed/12865930 http://dx.doi.org/10.1038/sj.bjc.6601022 Text en Copyright © 2003 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Experimental Therapeutics Abou El Hassan, M A I Verheul, H M W Jorna, A S Schalkwijk, C van Bezu, J van der Vijgh, W J F Bast, A The new cardioprotector Monohydroxyethylrutoside protects against doxorubicin-induced inflammatory effects in vitro |
title | The new cardioprotector Monohydroxyethylrutoside protects against doxorubicin-induced inflammatory effects in vitro |
title_full | The new cardioprotector Monohydroxyethylrutoside protects against doxorubicin-induced inflammatory effects in vitro |
title_fullStr | The new cardioprotector Monohydroxyethylrutoside protects against doxorubicin-induced inflammatory effects in vitro |
title_full_unstemmed | The new cardioprotector Monohydroxyethylrutoside protects against doxorubicin-induced inflammatory effects in vitro |
title_short | The new cardioprotector Monohydroxyethylrutoside protects against doxorubicin-induced inflammatory effects in vitro |
title_sort | new cardioprotector monohydroxyethylrutoside protects against doxorubicin-induced inflammatory effects in vitro |
topic | Experimental Therapeutics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2394271/ https://www.ncbi.nlm.nih.gov/pubmed/12865930 http://dx.doi.org/10.1038/sj.bjc.6601022 |
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