Please use this identifier to cite or link to this item: http://www.repositorio.ufop.br/handle/123456789/7444
Title: Hepatotoxicity of pentavalent antimonial drug : possible role of residual Sb(III) and protective effect of ascorbic acid.
Authors: Kato, Kelly Cristina
Teixeira, Eliane Morais
Reis, Priscila Gomes dos
Barcellos, Neila Marcia Silva
Salaün, Pascal
Campos, Paula Peixoto
Corrêa Junior, José Dias
Rabello, Ana
Demicheli, Cynthia Peres
Frezard, Frederic Jean Georges
Issue Date: 2013
Citation: KATO, K. C. et al. Hepatotoxicity of pentavalent antimonial drug: possible role of residual Sb(III) and protective effect of ascorbic acid. Antimicrobial Agents and Chemotherapy, v. 58, p. 481-488, 2013. Disponível em: <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3910754/pdf/zac481.pdf>. Acesso em: 10 jan. 2017.
Abstract: Pentavalent antimonial drugs such as meglumine antimoniate (Glucantime [Glu; Sanofi-Aventis, São Paulo, Brazil]) produce severe side effects, including cardiotoxicity and hepatotoxicity, during the treatment of leishmaniasis. We evaluated the role of residual Sb(III) in the hepatotoxicity of meglumine antimoniate, as well as the protective effect of the antioxidant ascorbic acid (AA) during antimonial chemotherapy in a murine model of visceral leishmaniasis. BALB/c mice infected with Leishmania infantum were treated intraperitoneally at 80 mg of Sb/kg/day with commercial meglumine antimoniate (Glu) or a synthetic meglumine antimoniate with lower Sb(III) level (MA), in association or not with AA (15 mg/kg/day), for a 20-day period. Control groups received saline or saline plus AA. Livers were evaluated for hepatocytes histological alterations, peroxidase activity, and apoptosis. Increased proportions of swollen and apoptotic hepatocytes were observed in animals treated with Glu compared to animals treated with saline or MA. The peroxidase activity was also enhanced in the liver of animals that received Glu. Cotreatment with AA reduced the extent of histological changes, the apoptotic index, and the peroxidase activity to levels corresponding to the control group. Moreover, the association with AA did not affect the hepatic uptake of Sb and the ability of Glu to reduce the liver and spleen parasite loads in infected mice. In conclusion, our data supports the use of pentavalent antimonials with low residue of Sb(III) and the association of pentavalent antimonials with AA, as effective strategies to reduce side effects in antimonial therapy.
URI: http://www.repositorio.ufop.br/handle/123456789/7444
metadata.dc.identifier.uri2: https://aac.asm.org/content/58/1/481
metadata.dc.identifier.doi: http://dx.doi.org/10.1128/AAC.01499-13
ISSN: 1098-6596
Appears in Collections:DEFAR - Artigos publicados em periódicos

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