Breitkreutz R, Babylon A, Hack V, Schuster K, Tokus M, Böhles H, Hagmüller E, Edler L, Holm E, Dröge W
Deutsches Krebsforschungszentrum, Division of Immunochemistry, Heidelberg, Germany.
Br J Cancer. 2000 Jan;82(2):399-403. doi: 10.1054/bjoc.1999.0933.
Abnormally low intramuscular glutamate and glutathione (GSH) levels and/or a decreased muscular uptake of glutamate by the skeletal muscle tissue have previously been found in malignant diseases and simian immunodeficiency virus (SIV) infection and may contribute to the development of cachexia. We tested the hypothesis that an impaired mitochondrial energy metabolism may compromise the Na+-dependent glutamate transport. A randomized double-blind clinical trial was designed to study the effects of L-carnitine, i.e. an agent known to enhance mitochondrial integrity and function, on the glutamate transport and plasma glutamate level of cancer patients. The effect of carnitine on the intramuscular glutamate and GSH levels was examined in complementary experiments with tumour-bearing mice. In the mice, L-carnitine treatment ameliorated indeed the tumour-induced decrease in muscular glutamate and GSH levels and the increase in plasma glutamate levels. The carnitine-treated group in the randomized clinical study showed also a significant decrease in the plasma glutamate levels but only a moderate and statistically not significant increase in the relative glutamate uptake in the lower extremities. Further studies may be warranted to determine the effect of L-carnitine on the intramuscular GSH levels in cancer patients.
先前在恶性疾病和猿猴免疫缺陷病毒（SIV）感染中发现，肌肉内谷氨酸和谷胱甘肽（GSH）水平异常低和/或骨骼肌组织对谷氨酸的肌肉摄取减少，这可能导致恶病质的发展。我们检验了线粒体能量代谢受损可能会损害钠依赖性谷氨酸转运的假设。设计了一项随机双盲临床试验，以研究L-肉碱（一种已知可增强线粒体完整性和功能的药物）对癌症患者谷氨酸转运和血浆谷氨酸水平的影响。在对荷瘤小鼠的补充实验中，研究了肉碱对肌肉内谷氨酸和GSH水平的影响。在小鼠中，L-肉碱治疗确实改善了肿瘤诱导的肌肉谷氨酸和GSH水平降低以及血浆谷氨酸水平升高。随机临床研究中的肉碱治疗组血浆谷氨酸水平也显著降低，但下肢相对谷氨酸摄取仅适度增加且无统计学意义。可能需要进一步研究以确定L-肉碱对癌症患者肌肉内GSH水平的影响。
