Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, Arkansas 72079, United States.
Office of Director, National Center for Toxicological Research/FDA, Jefferson, Arkansas 72079, United States.
Chem Res Toxicol. 2021 May 17;34(5):1208-1222. doi: 10.1021/acs.chemrestox.0c00479. Epub 2021 Feb 11.
Carnitine is an essential metabolite that is absorbed from the diet and synthesized in the kidney, liver, and brain. It ferries fatty acids across the mitochondrial membrane to undergo β-oxidation. Carnitine has been studied as a therapy or protective agent for many neurological diseases and neurotoxicity (e.g., prolonged anesthetic exposure-induced developmental neurotoxicity in preclinical models). Preclinical and clinical data support the notion that carnitine or acetyl carnitine may improve a patient's quality of life through increased mitochondrial respiration, release of neurotransmitters, and global gene expression changes, showing the potential of carnitine beyond its approved use to treat primary and secondary carnitine deficiency. In this review, we summarize the beneficial effects of carnitine or acetyl carnitine on the central nervous system, highlighting protective effects against neurotoxicity-induced damage caused by various chemicals and encouraging a thorough evaluation of carnitine use as a therapy for patients suffering from neurotoxicant exposure.
肉碱是一种必需的代谢物,可从饮食中吸收并在肾脏、肝脏和大脑中合成。它将脂肪酸转运穿过线粒体膜进行β-氧化。肉碱已被研究作为许多神经疾病和神经毒性的治疗或保护剂(例如,在临床前模型中延长麻醉暴露诱导的发育性神经毒性)。临床前和临床数据支持这样的观点,即肉碱或乙酰肉碱可能通过增加线粒体呼吸、神经递质释放和整体基因表达变化来提高患者的生活质量,显示出肉碱除了其批准用于治疗原发性和继发性肉碱缺乏症之外的潜在用途。在这篇综述中,我们总结了肉碱或乙酰肉碱对中枢神经系统的有益作用,强调了其对各种化学物质引起的神经毒性诱导损伤的保护作用,并鼓励对肉碱作为治疗神经毒性暴露患者的疗法进行全面评估。