Oxidative stress on cardiotoxicity after treatment with single and multiple doses of doxorubicin

Autor(es):Mostrar menos -

Pacifico de Freitas Segredo, M. ^[1] ; Favero Salvadori, D. M. ^[2] ; Rocha, N. S. ^[3] ; Fontes Moretto, F. C. ^[1] ; Correa, C. R. ^[1] ; Camargo, E. A. ^[2] ; de Almeida, D. C. ^[2] ; Silva Reis, R. A. ^[1] ; Murbach Freire, C. M. ^[2] ; Braz, M. G. ^[2] ; Tang, G. ^[4] ; Matsubara, L. S. ^[1] ; Matsubara, B. B. ^[1] ; Yeum, K-J ^[5] ; Ferreira, A. L. A. ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ UNESP, Dept Internal Med, Botucatu Med Sch, BR-18618970 Botucatu, SP - Brazil

^[2] Sao Paulo State Univ UNESP, Dept Pathol, Botucatu Med Sch, BR-18618970 Botucatu, SP - Brazil

^[3] Sao Paulo State Univ UNESP, Dept Clin Vet Med, Fac Vet Med, BR-18618970 Botucatu, SP - Brazil

^[4] Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 - USA

^[5] Konkuk Univ, Div Food Biosci, Coll Biomed & Hlth Sci, Chungju Si - South Korea

• Tipo de documento: Artigo Científico
• Fonte: HUMAN & EXPERIMENTAL TOXICOLOGY; v. 33, n. 7, p. 748-760, JUL 2014.
• Citações Web of Science: 12

Resumo

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. (AU)

• Processo FAPESP: 07/07455-2 - Avaliação evolutiva do estresse oxidativo cardíaco induzido pela doxorubicina em ratos: estudo do mecanismo de lesão
• Beneficiário: Ana Lucia do Anjos Ferreira
• Modalidade de apoio: Auxílio à Pesquisa - Regular