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Oxidative stress on cardiotoxicity after treatment with single and multiple doses of doxorubicin.
Segredo, M Pacifico de Freitas; Salvadori, D M Favero; Rocha, N S; Moretto, F C Fontes; Correa, C R; Camargo, E A; de Almeida, D C; Reis, R A Silva; Freire, C M Murbach; Braz, M G; Tang, G; Matsubara, L S; Matsubara, B B; Yeum, K-J; Ferreira, A L A.
Afiliación
  • Segredo MP; Department of Internal Medicine, Botucatu Medical School, São Paulo State University-UNESP, Botucatu, SP, Brazil.
  • Salvadori DM; Department of Pathology, Botucatu Medical School, São Paulo State University-UNESP, Botucatu, SP, Brazil.
  • Rocha NS; Department of Clinical Veterinary Medicine, Faculty of Veterinary Medicine, São Paulo State University-UNESP, Botucatu, SP, Brazil.
  • Moretto FC; Department of Internal Medicine, Botucatu Medical School, São Paulo State University-UNESP, Botucatu, SP, Brazil.
  • Correa CR; Department of Internal Medicine, Botucatu Medical School, São Paulo State University-UNESP, Botucatu, SP, Brazil.
  • Camargo EA; Department of Pathology, Botucatu Medical School, São Paulo State University-UNESP, Botucatu, SP, Brazil.
  • de Almeida DC; Department of Pathology, Botucatu Medical School, São Paulo State University-UNESP, Botucatu, SP, Brazil.
  • Reis RA; Department of Internal Medicine, Botucatu Medical School, São Paulo State University-UNESP, Botucatu, SP, Brazil.
  • Freire CM; Department of Pathology, Botucatu Medical School, São Paulo State University-UNESP, Botucatu, SP, Brazil.
  • Braz MG; Department of Pathology, Botucatu Medical School, São Paulo State University-UNESP, Botucatu, SP, Brazil.
  • Tang G; United States Department of Agriculture, Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.
  • Matsubara LS; Department of Internal Medicine, Botucatu Medical School, São Paulo State University-UNESP, Botucatu, SP, Brazil.
  • Matsubara BB; Department of Internal Medicine, Botucatu Medical School, São Paulo State University-UNESP, Botucatu, SP, Brazil.
  • Yeum KJ; Division of Food Bioscience, College of Biomedical and Health Sciences, Konkuk University, Chungju-si, South Korea.
  • Ferreira AL; Department of Internal Medicine, Botucatu Medical School, São Paulo State University-UNESP, Botucatu, SP, Brazil ferreira@fmb.unesp.br.
Hum Exp Toxicol ; 33(7): 748-60, 2014 Jul.
Article en En | MEDLINE | ID: mdl-24275640
The mechanism of doxorubicin (DOX)-induced cardiotoxicity remains controversial. Wistar rats (n = 66) received DOX injections intraperitoneally and were randomly assigned to 2 experimental protocols: (1) rats were killed before (-24 h, n = 8) and 24 h after (+24 h, n = 8) a single dose of DOX (4 mg/kg body weight) to determine the DOX acute effect and (2) rats (n = 58) received 4 injections of DOX (4 mg/kg body weight/week) and were killed before the first injection (M0) and 1 week after each injection (M1, M2, M3, and M4) to determine the chronological effects. Animals used at M0 (n = 8) were also used at moment -24 h of acute study. Cardiac total antioxidant performance (TAP), DNA damage, and morphology analyses were carried out at each time point. Single dose of DOX was associated with increased cardiac disarrangement, necrosis, and DNA damage (strand breaks (SBs) and oxidized pyrimidines) and decreased TAP. The chronological study showed an effect of a cumulative dose on body weight (R = -0.99, p = 0.011), necrosis (R = 1.00, p = 0.004), TAP (R = 0.95, p = 0.049), and DNA SBs (R = -0.95, p = 0.049). DNA SBs damage was negatively associated with TAP (R = -0.98, p = 0.018), and necrosis (R = -0.97, p = 0.027). Our results suggest that oxidative damage is associated with acute cardiotoxicity induced by a single dose of DOX only. Increased resistance to the oxidative stress is plausible for the multiple dose of DOX. Thus, different mechanisms may be involved in acute toxicity versus chronic toxicity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Doxorrubicina / Estrés Oxidativo / Miocitos Cardíacos / Cardiopatías / Antibióticos Antineoplásicos Límite: Animals Idioma: En Revista: Hum Exp Toxicol Asunto de la revista: TOXICOLOGIA Año: 2014 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Doxorrubicina / Estrés Oxidativo / Miocitos Cardíacos / Cardiopatías / Antibióticos Antineoplásicos Límite: Animals Idioma: En Revista: Hum Exp Toxicol Asunto de la revista: TOXICOLOGIA Año: 2014 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido