1 Boise State University, Boise, ID, USA.
2 University of South Carolina, Columbia, SC, USA.
Integr Cancer Ther. 2019 Jan-Dec;18:1534735419843999. doi: 10.1177/1534735419843999.
Doxorubicin (DOX) is a widely used chemotherapeutic agent with known cardiotoxic properties, while calorie restriction (CR) and exercise have well-documented cardioprotective effects. No studies have investigated the effects of CR alone or the combined effects of CR and exercise on DOX cardiotoxicity.
Rats were divided into 4 groups based on their food intake (ad libitum or CR) and activity (sedentary or voluntary wheel running [WR]). After completing a 16-week treatment, animals received either DOX (15 mg/kg) or saline (SAL) and cardiac function was measured 5 days after treatment. Chromatography was used to quantify left ventricular DOX accumulation.
Left ventricular developed pressure (LVDP), end systolic pressure (ESP), and left ventricular maximal rate of pressure development (dP/dt) were significantly higher in the CR + DOX group when compared with DOX. Fractional shortening, LVDP, ESP, dP/dt, and dP/dt were significantly higher in the CR + WR + DOX group compared with the DOX group. In addition, the CR + WR + DOX group showed significantly higher LVDP and ESP compared with the WR + DOX group. DOX accumulation in the heart was 5-fold lower ( P < .05) in the CR + WR + DOX group compared with the DOX group.
This is the first study to demonstrate that CR can reduce cardiac DOX accumulation, and confirms the protective role of CR against DOX-induced cardiac dysfunction. Our data also show that combining a known cardioprotective intervention, exercise training, with CR results in additive benefits in the protection against DOX cardiotoxicity.
多柔比星（DOX）是一种广泛应用的化疗药物，具有已知的心脏毒性；而热量限制（CR）和运动已被证实具有心脏保护作用。目前尚无研究调查单独的 CR 或 CR 与运动的联合作用对 DOX 心脏毒性的影响。
根据食物摄入（随意或 CR）和活动（久坐或自愿轮跑[WR]），将大鼠分为 4 组。完成 16 周的治疗后，动物接受 DOX（15mg/kg）或生理盐水（SAL）治疗，并在治疗后 5 天测量心脏功能。采用色谱法定量左心室 DOX 蓄积量。
与 DOX 组相比，CR+DOX 组的左心室发展压（LVDP）、收缩末期压（ESP）和左心室最大压力发展速率（dP/dt）显著升高。与 DOX 组相比，CR+WR+DOX 组的缩短分数、LVDP、ESP、dP/dt 和 dP/dt 显著升高。此外，CR+WR+DOX 组的 LVDP 和 ESP 明显高于 WR+DOX 组。与 DOX 组相比，CR+WR+DOX 组心脏中的 DOX 蓄积量降低了 5 倍（P<0.05）。
这是第一项研究表明 CR 可减少心脏中的 DOX 蓄积，并证实了 CR 对 DOX 诱导的心脏功能障碍的保护作用。我们的数据还表明，将已知的心脏保护干预措施（运动训练）与 CR 相结合可对 DOX 心脏毒性提供额外的保护。
