Genotoxicity assessment of the antimalarial compound artesunate in somatic cells of mice

Genotoxicity assessment of the antimalarial compound artesunate in somatic cells of mice

Author Aquino, Ivani Google Scholar
Perazzo, Fábio Ferreira Autor UNIFESP Google Scholar
Maistro, Edson Luis Google Scholar
Institution Univ Estadual Paulista
Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Abstract 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 B.V. All rights reserved.
Keywords Artesunate
Artemisinin derivate
Micronucleus test comet assay
Clastogenicity
Language English
Sponsor Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number CNPq: 306544/2006-7
FAPESP: 2008/51175-7
Date 2011-06-01
Published in Food and Chemical Toxicology. Oxford: Pergamon-Elsevier B.V., v. 49, n. 6, p. 1335-1339, 2011.
ISSN 0278-6915 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 1335-1339
Origin http://dx.doi.org/10.1016/j.fct.2011.03.016
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000291514800021
URI http://repositorio.unifesp.br/handle/11600/33716

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