Oxidative stress on cardiotoxicity after treatment with single and multiple doses of doxorubicin
Abstract
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 (M-0) and 1 week after each injection (M-1, M-2, M-3, and M4()) to determine the chronological effects. Animals used at M-0 (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.
How to cite this document
Language
Sponsor
Grant number

Related items
Showing items related by title, author, creator and subject.
-
Núcleos de Ensino da Unesp: artigos 2009
Pinho, Sheila Zambello de; Oliveira, José Brás Barreto de
; Gazola, Rodrigo José Cristiano
; Mazotti, Adriano César
; Molero, Camila Schimite
; Mendes, Carolina Borghi
; Mello, Denise Fernandes de
; Marques, Emilia de Mendonça Rosa
; Talamoni, Jandira Liria Biscalquini
; Silva, José Humberto Dias da
et al. (Coleção PROGRAD (UNESP), 2011) [Livro]
-
Núcleos de Ensino da Unesp: artigos 2008
Pinho, Sheila Zambello de; Oliveira, José Brás Barreto de
; Pontes, Sueli Rodrigues
; Almeida, Djanira Soares de Oliveira e
; Godoy, Kathya Maria Ayres de
; Rosa, Claudia de Souza
; Nunes, Julianus Araújo
; Salvador, Sérgio Azevedo
; David, Célia Maria
; Vilche Peña, Angel Fidel
et al. (Coleção PROGRAD (UNESP), 2011) [Livro]
-
Ser e tornar-se professor: práticas educativas no contexto escolar
Pinho, Sheila Zambello de; Spazziani, Maria de Lourdes
; Mendonça, Sueli Guadelupe de Lima
; Rubo, Elisabete Aparecida Andrello
; Villarreal, Dalva Maria de Oliveira
; Duarte, Camila
; Okamoto, Mary Yoko
; Souza, Thais R.
; Garms, Gilza Maria Zauhy
; Marin, Fátima Aparecida Dias Gomes
et al. (Coleção PROGRAD (UNESP), 2012) [Livro]