Abstract：
Mitochondrial dysfunction and excessive reactive oxygen species production contributes to the pathophysiology of aging. Coenzyme Q10 is thought to protect mitochondria from oxidative damage; thus, mitoquinone was developed as mitochondria-targeted analogue with similar antioxidant activity. Mitoquinone is the oxidized form of mitoquinol. Mitoquinone/mitoquinol mesylate has been proposed as a food ingredient. As part of the safety analysis, we performed genotoxicity assays and a 39-week toxicity study to determine overall toxicity potential. Mitoquinone mesylate showed no evidence of genotoxic potential in two in vitro assays, bacterial reverse mutation and human lymphocyte chromosome aberration, nor in the in vivo micronucleus test in rats. In the 39-week study in dogs, there were no findings observed, which were considered to represent adverse systemic toxicity; therefore, the high dose level (40 mg/kg/day) was considered the NOAEL. The principal findings in this study were fecal disturbances and vomiting. These findings were considered to be due to a local, possibly irritant effect of the test substance on the gastrointestinal tract and were not considered adverse as there were no impacts on clinical or histopathology. This highest dose exceeds the expected daily human intake more than 100-fold. Data from well-designed clinical trials actively collecting safety endpoints corroborate that 20 mg/day can be safely consumed and is not likely to result in significant gastrointestinal complaints. These results support the conclusion that the use of mitoquinone/mitoquinol mesylate as a food ingredient is safe.
摘要：
线粒体功能障碍和过量的活性氧产生有助于衰老的病理生理学。辅酶Q10被认为可以保护线粒体免受氧化损伤；因此，米托醌被开发为具有相似抗氧化活性的线粒体靶向类似物。米托醌是米托喹醇的氧化形式。已提出将米托醌/米托喹醇甲磺酸酯作为食品成分。作为安全分析的一部分,我们进行了基因毒性试验和一项为期39周的毒性研究,以确定总体毒性潜力.在两个体外测定中，甲磺酸米托醌没有显示遗传毒性潜力的证据，细菌回复突变和人类淋巴细胞染色体畸变,在大鼠体内微核试验中也没有。在为期39周的狗研究中，没有观察到任何发现，被认为代表不利的全身毒性；因此，高剂量水平（40mg/kg/天）被认为是NOAEL。这项研究的主要发现是粪便紊乱和呕吐。这些发现被认为是由于当地的，受试物质可能对胃肠道有刺激作用，不被认为是不利的，因为对临床或组织病理学没有影响。该最高剂量超过预期的每日人类摄入量100倍以上。积极收集安全性终点的精心设计的临床试验数据证实，每天20mg可以安全食用，不太可能导致严重的胃肠道不适。这些结果支持使用米托醌/米托喹醇甲磺酸酯作为食品成分是安全的结论。
