School of Sport and Exercise Science, University of Northern Colorado, Greeley, CO 80639, USA.
J Physiol Biochem. 2013 Jun;69(2):177-87. doi: 10.1007/s13105-012-0200-0. Epub 2012 Aug 14.
Cancer-related fatigue is a pervasive syndrome experienced by a majority of cancer patients undergoing treatment, and muscular dysfunction may be a key component in the development and progression of this syndrome. Doxorubicin (DOX) is a commonly used antineoplastic agent used in the treatment of many cancers. The purpose of this study was to determine the effect of DOX exposure on the function of cardiac, skeletal, and smooth muscle tissues and examine the role accumulation of DOX may play in this process. In these studies, rats were treated with DOX and measurements of cardiac, skeletal, and smooth muscle function were assessed 1, 3, and 5 days after exposure. All muscular tissues showed significant and severe dysfunction, yet there was heterogeneity both in the time course of dysfunction and in the accumulation of DOX. Cardiac and skeletal muscle exhibited a time-dependent progressive decline in function during the 5 days following DOX treatment. In contrast, vascular function showed a decline in function that could be characterized as rapid onset and was sustained for the duration of the 5-day observation period. DOX accumulation was greatest in cardiac tissue, yet all muscular tissues showed a similar degree of dysfunction. Our data suggest that in muscular tissues both DOX-dependent and DOX-independent mechanisms may be involved with the muscular dysfunction observed following DOX treatment. Furthermore, this study highlights the fact that dysfunction of skeletal and smooth muscle may be an underappreciated aspect of DOX toxicity and may be a key component of cancer-related fatigue in these patients.
癌症相关性疲劳是大多数接受治疗的癌症患者普遍经历的一种综合征，肌肉功能障碍可能是该综合征发展和进展的关键组成部分。阿霉素（DOX）是一种常用于治疗多种癌症的常用抗肿瘤药物。本研究旨在确定 DOX 暴露对心脏、骨骼和平滑肌组织功能的影响，并探讨 DOX 积累在这一过程中可能发挥的作用。在这些研究中，大鼠接受 DOX 治疗，并在暴露后 1、3 和 5 天评估心脏、骨骼和平滑肌功能的测量值。所有肌肉组织均表现出明显且严重的功能障碍，但在功能障碍的时间过程和 DOX 的积累方面存在异质性。心脏和骨骼肌在 DOX 治疗后 5 天内表现出功能的时间依赖性进行性下降。相比之下，血管功能表现出快速发作和持续 5 天观察期的功能下降。DOX 在心脏组织中的积累最大，但所有肌肉组织均表现出相似程度的功能障碍。我们的数据表明，在肌肉组织中，DOX 依赖性和 DOX 非依赖性机制可能都与 DOX 治疗后观察到的肌肉功能障碍有关。此外，本研究强调了这样一个事实，即骨骼和平滑肌功能障碍可能是 DOX 毒性被低估的一个方面，并且可能是这些患者癌症相关性疲劳的关键组成部分。
