Reduction of atherosclerotic lesions in rabbits treated with etoposide associated with cholesterol-rich nanoemulsions

Elaine R Tavares1, Fatima R Freitas1, Jayme Diament1, Raul C Maranh&atilde;o1,21Heart Institute of the Medical School Hospital (InCor), University of S&atilde;o Paulo, S&atilde;o Paulo, Brazil; 2Faculty of Pharmaceutical Sciences, University of S&atilde;o Paulo, S&...

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Autores principales:	Tavares ER, Freitas FR, Diament JD, Maranh&atilde;o RC
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/77c49023b15a461bacc1b02bd73b8080
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spelling	oai:doaj.org-article:77c49023b15a461bacc1b02bd73b80802021-12-02T00:21:17ZReduction of atherosclerotic lesions in rabbits treated with etoposide associated with cholesterol-rich nanoemulsions1176-91141178-2013https://doaj.org/article/77c49023b15a461bacc1b02bd73b80802011-10-01T00:00:00Zhttp://www.dovepress.com/reduction-of-atherosclerotic-lesions-in-rabbits-treated-with-etoposide-a8462https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Elaine R Tavares1, Fatima R Freitas1, Jayme Diament1, Raul C Maranh&atilde;o1,21Heart Institute of the Medical School Hospital (InCor), University of S&atilde;o Paulo, S&atilde;o Paulo, Brazil; 2Faculty of Pharmaceutical Sciences, University of S&atilde;o Paulo, S&atilde;o Paulo, BrazilObjectives: Cholesterol-rich nanoemulsions (LDE) bind to low-density lipoprotein (LDL) receptors and after injection into the bloodstream concentrate in aortas of atherosclerotic rabbits. Association of paclitaxel with LDE markedly reduces the lesions. In previous studies, treatment of refractory cancer patients with etoposide associated with LDE had been shown devoid of toxicity. In this study, the ability of etoposide to reduce lesions and inflammatory factors in atherosclerotic rabbits was investigated.Methods: Eighteen New Zealand rabbits were fed a 1% cholesterol diet for 60 days. Starting from day 30, nine animals were treated with four weekly intravenous injections of etoposide oleate (6 mg/kg) associated with LDE, and nine control animals were treated with saline solution injections.Results: LDE-etoposide reduced the lesion areas of cholesterol-fed animals by 85% and intima width by 50% and impaired macrophage and smooth muscle cell invasion of the intima. Treatment also markedly reduced the protein expression of lipoprotein receptors (LDL receptor, LDL-related protein-1, cluster of differentiation 36, and scavenger receptor class B member 1), inflammatory cytokines (interleukin-1&beta; and tumor necrosis factor-&alpha;), matrix metallopeptidase-9, and cell proliferation markers (topoisomerase II&alpha; and tubulin).Conclusion: The ability of LDE-etoposide to strongly reduce the lesion area and the inflammatory process warrants the great therapeutic potential of this novel preparation to target the inflammatory-proliferative basic mechanisms of the disease.Keywords: atherosclerosis treatment, drug delivery, LDL-receptorsTavares ERFreitas FRDiament JDMaranh&atilde;o RCDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2011, Iss default, Pp 2297-2304 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Tavares ER Freitas FR Diament JD Maranh&atilde;o RC Reduction of atherosclerotic lesions in rabbits treated with etoposide associated with cholesterol-rich nanoemulsions
description	Elaine R Tavares1, Fatima R Freitas1, Jayme Diament1, Raul C Maranh&atilde;o1,21Heart Institute of the Medical School Hospital (InCor), University of S&atilde;o Paulo, S&atilde;o Paulo, Brazil; 2Faculty of Pharmaceutical Sciences, University of S&atilde;o Paulo, S&atilde;o Paulo, BrazilObjectives: Cholesterol-rich nanoemulsions (LDE) bind to low-density lipoprotein (LDL) receptors and after injection into the bloodstream concentrate in aortas of atherosclerotic rabbits. Association of paclitaxel with LDE markedly reduces the lesions. In previous studies, treatment of refractory cancer patients with etoposide associated with LDE had been shown devoid of toxicity. In this study, the ability of etoposide to reduce lesions and inflammatory factors in atherosclerotic rabbits was investigated.Methods: Eighteen New Zealand rabbits were fed a 1% cholesterol diet for 60 days. Starting from day 30, nine animals were treated with four weekly intravenous injections of etoposide oleate (6 mg/kg) associated with LDE, and nine control animals were treated with saline solution injections.Results: LDE-etoposide reduced the lesion areas of cholesterol-fed animals by 85% and intima width by 50% and impaired macrophage and smooth muscle cell invasion of the intima. Treatment also markedly reduced the protein expression of lipoprotein receptors (LDL receptor, LDL-related protein-1, cluster of differentiation 36, and scavenger receptor class B member 1), inflammatory cytokines (interleukin-1&beta; and tumor necrosis factor-&alpha;), matrix metallopeptidase-9, and cell proliferation markers (topoisomerase II&alpha; and tubulin).Conclusion: The ability of LDE-etoposide to strongly reduce the lesion area and the inflammatory process warrants the great therapeutic potential of this novel preparation to target the inflammatory-proliferative basic mechanisms of the disease.Keywords: atherosclerosis treatment, drug delivery, LDL-receptors
format	article
author	Tavares ER Freitas FR Diament JD Maranh&atilde;o RC
author_facet	Tavares ER Freitas FR Diament JD Maranh&atilde;o RC
author_sort	Tavares ER
title	Reduction of atherosclerotic lesions in rabbits treated with etoposide associated with cholesterol-rich nanoemulsions
title_short	Reduction of atherosclerotic lesions in rabbits treated with etoposide associated with cholesterol-rich nanoemulsions
title_full	Reduction of atherosclerotic lesions in rabbits treated with etoposide associated with cholesterol-rich nanoemulsions
title_fullStr	Reduction of atherosclerotic lesions in rabbits treated with etoposide associated with cholesterol-rich nanoemulsions
title_full_unstemmed	Reduction of atherosclerotic lesions in rabbits treated with etoposide associated with cholesterol-rich nanoemulsions
title_sort	reduction of atherosclerotic lesions in rabbits treated with etoposide associated with cholesterol-rich nanoemulsions
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/77c49023b15a461bacc1b02bd73b8080
work_keys_str_mv	AT tavareser reductionofatheroscleroticlesionsinrabbitstreatedwithetoposideassociatedwithcholesterolrichnanoemulsions AT freitasfr reductionofatheroscleroticlesionsinrabbitstreatedwithetoposideassociatedwithcholesterolrichnanoemulsions AT diamentjd reductionofatheroscleroticlesionsinrabbitstreatedwithetoposideassociatedwithcholesterolrichnanoemulsions AT maranhampatildeorc reductionofatheroscleroticlesionsinrabbitstreatedwithetoposideassociatedwithcholesterolrichnanoemulsions
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Reduction of atherosclerotic lesions in rabbits treated with etoposide associated with cholesterol-rich nanoemulsions

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