Doxorubicin (DOX) is a commonly used chemotherapeutic drug that may induce a dose limiting cardiomyopathy. Cytotoxic effects of DOX are related to its ability to undergo redox cycling, resulting in superoxide anion generation and mitochondrial injury. The apoA‐I mimetic peptide 4F exerts anti‐oxidant effects by improving functional properties of HDL and by upregulating the enzyme superoxide dismutase (SOD). In this study, we tested the hypothesis that 4F treatment attenuates cardiac dysfunction in DOX‐treated rats. Male Sprauge‐Dawley rats were pre‐treated with 4F (5mg/kg/day) or saline by ip injection for 5 days. LV function was measured on day 5 in 4F‐ and saline‐treated rats by echocardiography. DOX (20mg/kg) was then administered by ip injection and echo measurements repeated on day 9. A separate CONTROL group received ip saline over the same time period. Stroke volume (SV) and ejection fraction (EF) were reduced by 25 ± 2% and 44 ± 7% respectively in DOX+saline rats (n=8) on day 9 compared to CONTROL rats (n=10). In contrast, the reduction in SV (8 ± 3%) and EF (7 ± 4%) was significantly attenuated in DOX+4F rats (n=8). It is proposed that a cardioprotective mechanism of 4F is likely due to the induction of SOD resulting in increased scavenging of DOX‐generated superoxide anion. In ongoing experiments, cardiac levels of SOD protein and mRNA expression are being assessed in DOX rats treated with saline or 4F.
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