Genotoxicity assessment of the antimalarial compound artesunate in somatic cells of mice
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.fct.2011.03.016 http://hdl.handle.net/11449/10814 |
Resumo: | Artesunate is a derivate of artemisinin that is both an antimalarial agent and acts cytotoxically on tumor cells. Despite its therapeutic use, its in vivo genotoxic potential has still not been evaluated. This study, therefore, was an investigation into the effects of a single oral administration of artesunate with an in vivo comet assay that analyzed leukocytes from peripheral blood and liver cells, and a micronucleus (MN) assay of bone marrow cells from male Swiss mice. The artesunate was administered by oral gavage at doses of 5, 50 and 100 mg/kg. Cytotoxicity was assessed by scoring 200 consecutive polychromatic (PCE) and normochromatic (NCE) erythrocytes (PCE/NCE ratio). The results demonstrate that artesunate induced significant DNA damage only in liver cells and that high doses of artesunate caused an increase in the mean number of micronucleated polychromatic erythrocytes (MNPCE). Under our experimental conditions, artesunate showed weak genotoxic effects at low doses and clastogenic effects at high doses. The PCE/NCE ratio indicated no cytotoxicity. The data obtained suggest caution about either continuous or high-dose use of artesunate by humans. (C) 2011 Elsevier Ltd. All rights reserved. |
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Genotoxicity assessment of the antimalarial compound artesunate in somatic cells of miceArtesunateArtemisinin derivateMicronucleus test comet assayClastogenicityArtesunate is a derivate of artemisinin that is both an antimalarial agent and acts cytotoxically on tumor cells. Despite its therapeutic use, its in vivo genotoxic potential has still not been evaluated. This study, therefore, was an investigation into the effects of a single oral administration of artesunate with an in vivo comet assay that analyzed leukocytes from peripheral blood and liver cells, and a micronucleus (MN) assay of bone marrow cells from male Swiss mice. The artesunate was administered by oral gavage at doses of 5, 50 and 100 mg/kg. Cytotoxicity was assessed by scoring 200 consecutive polychromatic (PCE) and normochromatic (NCE) erythrocytes (PCE/NCE ratio). The results demonstrate that artesunate induced significant DNA damage only in liver cells and that high doses of artesunate caused an increase in the mean number of micronucleated polychromatic erythrocytes (MNPCE). Under our experimental conditions, artesunate showed weak genotoxic effects at low doses and clastogenic effects at high doses. The PCE/NCE ratio indicated no cytotoxicity. The data obtained suggest caution about either continuous or high-dose use of artesunate by humans. (C) 2011 Elsevier Ltd. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ Estadual Paulista, UNESP, Fac Filosofia & Ciencias, Dept Fonoaudiol, BR-17525900 Marilia, SP, BrazilUniv Estadual Paulista, UNESP, Inst Biociencias, Programa Posgrad Biol Geral & Aplicada, BR-18618970 Botucatu, SP, BrazilUniv Fed São Paulo Unifesp, Dept Ciencias Exatas & Terra, BR-09972270 Diadema, SP, BrazilUniv Estadual Paulista, UNESP, Fac Filosofia & Ciencias, Dept Fonoaudiol, BR-17525900 Marilia, SP, BrazilUniv Estadual Paulista, UNESP, Inst Biociencias, Programa Posgrad Biol Geral & Aplicada, BR-18618970 Botucatu, SP, BrazilCNPq: 306544/2006-7FAPESP: 08/51175-7Pergamon-Elsevier B.V. LtdUniversidade Estadual Paulista (Unesp)Universidade Federal de São Paulo (UNIFESP)Aquino, Ivani [UNESP]Perazzo, Fabio FerreiraMaistro, Edson Luis [UNESP]2014-05-20T13:31:45Z2014-05-20T13:31:45Z2011-06-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1335-1339application/pdfhttp://dx.doi.org/10.1016/j.fct.2011.03.016Food and Chemical Toxicology. Oxford: Pergamon-Elsevier B.V. Ltd, v. 49, n. 6, p. 1335-1339, 2011.0278-6915http://hdl.handle.net/11449/1081410.1016/j.fct.2011.03.016WOS:000291514800021WOS000291514800021.pdf47875216130383150000-0003-0757-7876Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengFood and Chemical Toxicology3.9771,144info:eu-repo/semantics/openAccess2024-08-09T17:40:18Zoai:repositorio.unesp.br:11449/10814Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-09T17:40:18Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Genotoxicity assessment of the antimalarial compound artesunate in somatic cells of mice |
title |
Genotoxicity assessment of the antimalarial compound artesunate in somatic cells of mice |
spellingShingle |
Genotoxicity assessment of the antimalarial compound artesunate in somatic cells of mice Aquino, Ivani [UNESP] Artesunate Artemisinin derivate Micronucleus test comet assay Clastogenicity |
title_short |
Genotoxicity assessment of the antimalarial compound artesunate in somatic cells of mice |
title_full |
Genotoxicity assessment of the antimalarial compound artesunate in somatic cells of mice |
title_fullStr |
Genotoxicity assessment of the antimalarial compound artesunate in somatic cells of mice |
title_full_unstemmed |
Genotoxicity assessment of the antimalarial compound artesunate in somatic cells of mice |
title_sort |
Genotoxicity assessment of the antimalarial compound artesunate in somatic cells of mice |
author |
Aquino, Ivani [UNESP] |
author_facet |
Aquino, Ivani [UNESP] Perazzo, Fabio Ferreira Maistro, Edson Luis [UNESP] |
author_role |
author |
author2 |
Perazzo, Fabio Ferreira Maistro, Edson Luis [UNESP] |
author2_role |
author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Universidade Federal de São Paulo (UNIFESP) |
dc.contributor.author.fl_str_mv |
Aquino, Ivani [UNESP] Perazzo, Fabio Ferreira Maistro, Edson Luis [UNESP] |
dc.subject.por.fl_str_mv |
Artesunate Artemisinin derivate Micronucleus test comet assay Clastogenicity |
topic |
Artesunate Artemisinin derivate Micronucleus test comet assay Clastogenicity |
description |
Artesunate is a derivate of artemisinin that is both an antimalarial agent and acts cytotoxically on tumor cells. Despite its therapeutic use, its in vivo genotoxic potential has still not been evaluated. This study, therefore, was an investigation into the effects of a single oral administration of artesunate with an in vivo comet assay that analyzed leukocytes from peripheral blood and liver cells, and a micronucleus (MN) assay of bone marrow cells from male Swiss mice. The artesunate was administered by oral gavage at doses of 5, 50 and 100 mg/kg. Cytotoxicity was assessed by scoring 200 consecutive polychromatic (PCE) and normochromatic (NCE) erythrocytes (PCE/NCE ratio). The results demonstrate that artesunate induced significant DNA damage only in liver cells and that high doses of artesunate caused an increase in the mean number of micronucleated polychromatic erythrocytes (MNPCE). Under our experimental conditions, artesunate showed weak genotoxic effects at low doses and clastogenic effects at high doses. The PCE/NCE ratio indicated no cytotoxicity. The data obtained suggest caution about either continuous or high-dose use of artesunate by humans. (C) 2011 Elsevier Ltd. All rights reserved. |
publishDate |
2011 |
dc.date.none.fl_str_mv |
2011-06-01 2014-05-20T13:31:45Z 2014-05-20T13:31:45Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.fct.2011.03.016 Food and Chemical Toxicology. Oxford: Pergamon-Elsevier B.V. Ltd, v. 49, n. 6, p. 1335-1339, 2011. 0278-6915 http://hdl.handle.net/11449/10814 10.1016/j.fct.2011.03.016 WOS:000291514800021 WOS000291514800021.pdf 4787521613038315 0000-0003-0757-7876 |
url |
http://dx.doi.org/10.1016/j.fct.2011.03.016 http://hdl.handle.net/11449/10814 |
identifier_str_mv |
Food and Chemical Toxicology. Oxford: Pergamon-Elsevier B.V. Ltd, v. 49, n. 6, p. 1335-1339, 2011. 0278-6915 10.1016/j.fct.2011.03.016 WOS:000291514800021 WOS000291514800021.pdf 4787521613038315 0000-0003-0757-7876 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Food and Chemical Toxicology 3.977 1,144 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
1335-1339 application/pdf |
dc.publisher.none.fl_str_mv |
Pergamon-Elsevier B.V. Ltd |
publisher.none.fl_str_mv |
Pergamon-Elsevier B.V. Ltd |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
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1808128215233855488 |