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

Abstract

<jats:p> 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<jats:sub>0</jats:sub>) and 1 week after each injection (M<jats:sub>1</jats:sub>, M<jats:sub>2</jats:sub>, M<jats:sub>3</jats:sub>, and M<jats:sub>4</jats:sub>) to determine the chronological effects. Animals used at M<jats:sub>0</jats:sub> ( 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. </jats:p>

Sex-dependent alteration of cardiac cytochrome P450 gene expression by doxorubicin in C57Bl/6 mice

“…Several mechanisms have been postulated to explain sexual dimorphism of chronic DOX-induced cardiotoxicity including differences in myocardial energy metabolism, mast cell activation, and cardiolipin remodeling [11, 12, 14]. Since the mechanisms of acute DOX-induced cardiotoxicity may be different from those of chronic cardiotoxicity [17], it is important to investigate the mechanisms of sex-related differences in acute DOX-induced cardiotoxicity.…”

Pamidronate Attenuates Oxidative Stress and Energetic Metabolism Changes but Worsens Functional Outcomes in Acute Doxorubicin-Induced Cardiotoxicity in Rats

“…Some mechanisms are simultaneously involved in cardiotoxicity that is induced by doxorubicin, such as matrix metalloproteinases (MMP)-2 activation [4,6], and an increase in oxidative stress [7,8].…”

Combination of quercetin and Adriamycin effectively suppresses the growth of refractory acute leukemia

“…however, with the increase in the dose of Adriamycin, its toxic side effects became more severe. The most severe side effect is cardiac injury (7,28). A previous study has found that administering Adriamycin to BALB/c nude mice transplanted with the leukemic cell line P388 causes cardiac injury, which is alleviated following co-treatment with Adriamycin and quercetin (12).…”

“…A previous study has found that administering Adriamycin to BALB/c nude mice transplanted with the leukemic cell line P388 causes cardiac injury, which is alleviated following co-treatment with Adriamycin and quercetin (12). The mechanism underlying the cardiac toxicity of Adriamycin may be oxidative damage to cardiomyocytes, which is associated with various types of heart injury (24,28). SOD scavenges superoxide radicals in cells to protect them from damage.…”