Terrill Jessica R, Pinniger Gavin J, Nair Keshav V, Grounds Miranda D, Arthur Peter G
School of Molecular Sciences, the University of Western Australia, Perth, Western Australia, Australia.
School of Human Sciences, the University of Western Australia, Perth, Western Australia, Australia.
PLoS One. 2017 Nov 2;12(11):e0187317. doi: 10.1371/journal.pone.0187317. eCollection 2017.
Duchenne Muscular Dystrophy (DMD) is a fatal muscle wasting disease manifested in young boys, for which there is no current cure. We have shown that the amino acid taurine is safe and effective at preventing dystropathology in the mdx mouse model for DMD. This study aimed to establish if treating growing mdx mice with a higher dose of taurine was more effective at improving strength and reducing inflammation and oxidative stress. Mice were treated with a dose of taurine estimated to be 16 g/kg/day, in drinking water from 1-6 weeks of age, after which in vivo and ex vivo muscle strength was assessed, as were measures of inflammation, oxidative stress and taurine metabolism. While the dose did decrease inflammation and protein oxidation in dystrophic muscles, there was no improvement in muscle strength (in contrast with benefits observed with the lower dose) and growth of the young mice was significantly restricted. We present novel data that a high taurine dose increases the cysteine content of both mdx liver and plasma, a possible result of down regulation of the taurine synthesis pathway in the liver (which functions to dispose of excess cysteine, which is toxic). These data caution that a high dose of taurine can have adverse effects and may be less efficacious than lower taurine doses. Therefore, monitoring of taurine dosage needs to be considered in future pre-clinical trials, in anticipation of using taurine as a clinical therapy for growing DMD boys (and other conditions).
杜氏肌营养不良症（DMD）是一种在幼年男孩中表现出的致命性肌肉萎缩疾病，目前尚无治愈方法。我们已经表明，氨基酸牛磺酸在杜氏肌营养不良症的mdx小鼠模型中预防肌营养不良病理方面是安全有效的。本研究旨在确定用更高剂量的牛磺酸治疗生长中的mdx小鼠在改善力量、减轻炎症和氧化应激方面是否更有效。小鼠从1至6周龄开始饮用含有估计剂量为16克/千克/天牛磺酸的水进行治疗，之后评估体内和体外肌肉力量，以及炎症、氧化应激和牛磺酸代谢的指标。虽然该剂量确实降低了营养不良肌肉中的炎症和蛋白质氧化，但肌肉力量没有改善（与较低剂量观察到的益处相反），并且幼鼠的生长受到显著限制。我们提供了新的数据，即高剂量牛磺酸会增加mdx肝脏和血浆中的半胱氨酸含量，这可能是肝脏中牛磺酸合成途径下调的结果（该途径的作用是处理过量的、有毒的半胱氨酸）。这些数据警示，高剂量牛磺酸可能产生不良影响，并且可能不如低剂量牛磺酸有效。因此，在未来的临床前试验中，预计将牛磺酸用作生长中的杜氏肌营养不良症男孩（以及其他病症）的临床治疗方法时，需要考虑监测牛磺酸剂量。
