Using mass spectrometry-based targeted metabolomics, we aimed to determine the pattern of cardiac metabolic reprogramming and energetics in doxorubicin-induced heart failure. More importantly, we aimed to identify the potential effects of melatonin on cardiac metabolic reprogramming and energetics in doxorubicin-induced heart failure. Male Wistar rats (n = 18) were randomly divided into three groups (n = 6/group) to receive either (1) normal saline solution as a control, (2) 3 mg/kg/day of doxorubicin on Days 0, 4, 8, 15, 22, and 29, or (3) 3 mg/kg/day of doxorubicin on Days 0, 4, 8, 15, 22, and 29 plus 10 mg/kg/day of melatonin on Days 0–29. On Day 30, echocardiography was carried out and heart rate variability was analyzed for the evaluation of cardiac function. The rats were euthanized on the following day to enable the collection of ventricular cardiac tissue. Compared to the control group, the hearts of rats treated with doxorubicin alone exhibited impaired cardiac function, increased glucose and ketone body utilization, decreased fat utilization, decreased succinate oxidation, and decreased production of adenosine triphosphate. The cotreatment with melatonin could restore cardiac function, glucose and ketone body utilization, and adenosine triphosphate production in the heart. Interestingly, the cotreatment with melatonin led to an increase in cardiac fatty acid oxidation, branched-chain amino acid catabolism, and anaplerosis. All of these findings highlighted the potential efficacy of melatonin with regard to cardiac metabolic reprogramming and energetics. Our findings also suggested that melatonin could be considered as an adjunctive treatment for doxorubicin-induced heart failure in clinical practice.

中文翻译：

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褪黑素对阿霉素诱导心力衰竭大鼠心脏代谢重编程的影响：潜在治疗靶点的代谢组学研究

使用基于质谱的靶向代谢组学，我们的目的是确定阿霉素诱导的心力衰竭中心脏代谢重编程和能量学的模式。更重要的是，我们的目的是确定褪黑激素对阿霉素诱导的心力衰竭的心脏代谢重编程和能量学的潜在影响。雄性Wistar大鼠（n  =18）随机分为三组（n =18） = 6/组）接受（1）生理盐水溶液作为对照，（2）第0、4、8、15、22和29天3毫克/公斤/天的阿霉素，或（3）3毫克/kg/天的阿霉素（第 0、4、8、15、22 和 29 天）加上 10 mg/kg/天的褪黑激素（第 0-29 天）。第30天，进行超声心动图检查并分析心率变异性以评价心功能。第二天对大鼠实施安乐死，以收集心室心脏组织。与对照组相比，仅用阿霉素治疗的大鼠心脏表现出心功能受损、葡萄糖和酮体利用率增加、脂肪利用率降低、琥珀酸氧化减少以及三磷酸腺苷产生减少。与褪黑激素联合治疗可恢复心脏功能、葡萄糖和酮体利用，和心脏中三磷酸腺苷的产生。有趣的是，与褪黑激素联合治疗导致心脏脂肪酸氧化、支链氨基酸分解代谢和回补增加。所有这些发现都强调了褪黑激素在心脏代谢重编程和能量学方面的潜在功效。我们的研究结果还表明，在临床实践中，褪黑激素可以被视为阿霉素引起的心力衰竭的辅助治疗。