骨肌肉线粒体代谢物中克洛法齐明介导的,与年龄相关的变化
Jennifer Diaz-Espinosa1, Kathleen A Stringer2,3,4, Gus R Rosania1
1Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, MI 48109, USA.
Metabolites
|May 26, 2023
概括
老化的线粒体增加了对药物毒性的敏感性,特别是在骨肌肉中. 像l-carnitine这样的血液代谢物不反映这些与年龄相关的线粒体变化或预测不良药物反应.
科学领域:
- 老年学是指老年学的学科.
- 线粒体生物学 线粒体生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 线粒体健康随着年龄的增长而恶化,影响诸如心脏和骨肌肉等组织.
- 老化的线粒体可能会增加对药物不良反应 (ADRs) 的敏感性.
研究的目的:
- 评估线粒体代谢功能,并确定与年龄相关的药物诱导变化的生物标志物.
- 调查l-卡尼丁和乙卡尼丁作为生物标志物的有效性.
主要方法:
- 给年轻和老老的小鼠服用克洛法齐明 (CFZ) 或载体8周.
- 分析血液,心脏和骨肌肉的代谢物和CFZ水平.
- 使用跑步机测试测量肌肉功能.
主要成果:
- 在老老小鼠中,CFZ治疗导致体重减轻和改变耐力和骨肌肉线粒体代谢物.
- 没有观察到血液或心脏卡尼丁水平的显著变化.
- 骨肌中的药物诱导的线粒体变化没有反映在血液代谢产物中.
结论:
- 骨肌肉表现出与年龄相关的对线粒体药物毒性的敏感性.
- 血液中的l-卡尼丁和乙卡尼丁水平不是药物诱导的骨肌中的线粒体变化的可靠生物标志物.
- 肌肉功能和代谢可能更适合评估老年人ADR风险.
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