Clofazimine-Mediated, Age-Related Changes in Skeletal Muscle Mitochondrial Metabolites.
Clofazimine-Mediated, Age-Related Changes in Skeletal Muscle Mitochondrial Metabolites.
复制标题
氯富唑介导的骨骼肌线粒体代谢产物的年龄相关的变化。
DOI：
10.3390/metabo13050671
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发表时间：
2023-05-19
期刊：
影响因子：
4.1
通讯作者：
中科院分区：
文献类型：
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作者：
线粒体健康随着年龄的增长而下降，老年患者可以在富含线粒体的组织中表现出功能障碍，如心脏和骨骼肌。老化的线粒体可能使老年人更容易发生药物不良反应（ADR）。我们通过测量两种代谢物（l-肉碱和乙酰肉碱）来评估线粒体代谢功能，以确定其作为年龄相关的、药物诱导的线粒体代谢改变的候选临床生物标志物的有效性。为了研究线粒体代谢中与年龄和药物相关的变化，我们给年轻（4周龄）和老年（61周龄）雄性C57 BL/6 J小鼠施用FDA批准的亲脂性药物氯法齐明（CFZ）或溶剂8周。在治疗结束时，分析全血和心脏和骨骼肌的l-肉碱，乙酰肉碱和CFZ水平;肌肉功能通过跑步机测试测量。没有发现CFZ治疗的小鼠的血液或心脏肉毒碱水平的差异，但CFZ治疗的小鼠显示体重减轻，耐力和骨骼肌线粒体代谢产物水平的改变。这些发现证明了骨骼肌对线粒体药物毒性的年龄相关易感性。由于药物诱导的骨骼肌线粒体代谢的改变在血液中没有通过l-肉碱或乙酰肉碱水平反映出来，药物诱导的catabolism和肌肉功能的变化似乎与ADR风险增加的分层个体更相关。
Mitochondrial health declines with age, and older patients can demonstrate dysfunction in mitochondrial-rich tissues, such as cardiac and skeletal muscle. Aged mitochondria may make older adults more susceptible to adverse drug reactions (ADRs). We assessed mitochondrial metabolic function by measuring two metabolites, l-carnitine and acetylcarnitine, to determine their effectiveness as candidate clinical biomarkers for age-related, drug-induced alterations in mitochondrial metabolism. To study age- and medication-related changes in mitochondrial metabolism, we administered the FDA-approved mitochondriotropic drug, clofazimine (CFZ), or vehicle for 8 weeks to young (4-week-old) and old (61-week-old) male C57BL/6J mice. At the end of treatment, whole blood and cardiac and skeletal muscle were analyzed for l-carnitine, acetylcarnitine, and CFZ levels; muscle function was measured via a treadmill test. No differences were found in blood or cardiac carnitine levels of CFZ-treated mice, but CFZ-treated mice displayed lost body mass and alterations in endurance and levels of skeletal muscle mitochondrial metabolites. These findings demonstrate the age-related susceptibility of the skeletal muscle to mitochondria drug toxicity. Since drug-induced alterations in mitochondrial metabolism in skeletal muscle were not reflected in the blood by l-carnitine or acetylcarnitine levels, drug-induced catabolism and changes in muscle function appear more relevant to stratifying individuals at increased risk for ADRs.
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影响因子：
--
作者：
Bashiri Dezfouli A;Pourfathollah AA;Salar-Amoli J;Khosravi M;Nikogoftar-Zarif M;Yazdi M;Ali-Esfahani T
通讯作者：
Ali-Esfahani T
影响因子：
4.5
作者：
Flanagan JL;Simmons PA;Vehige J;Willcox MD;Garrett Q
通讯作者：
Garrett Q
影响因子：
4.9
作者：
Baik, Jason;Stringer, Kathleen A.;Rosania, Gus R.
通讯作者：
Rosania, Gus R.
影响因子：
16.6
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通讯作者：
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影响因子：
8.4
作者：
Bartel, Karin;Pein, Helmut;von Schwarzenberg, Karin
通讯作者：
von Schwarzenberg, Karin