Li Xuesen, Liu Zhongbo, Luo Cheng, Jia Haiqun, Sun Lijuan, Hou Bei, Shen Weili, Packer Lester, Cotman Carl W, Liu Jiankang
Institute for Nutritional Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Free Radic Biol Med. 2008 Apr 1;44(7):1465-74. doi: 10.1016/j.freeradbiomed.2008.01.004. Epub 2008 Jan 18.
alpha-Lipoic acid (LA) has been widely studied as an agent for preventing and treating various diseases associated with oxidative disruption of mitochondrial functions. To investigate a related mitochondrial antioxidant, we compared the effects of lipoamide (LM), the neutral amide of LA, with LA for measures of oxidative damage and mitochondrial dysfunction in a human retinal pigment epithelial (RPE) cell line. Acrolein, a major component of cigarette smoke and a product of lipid peroxidation, was used to induce oxidative mitochondrial damage in RPE cells. Overall, using comparable concentrations, LM was more effective than LA at preventing acrolein-induced mitochondrial dysfunction and oxidative stress. Relative to LA, LM improved ATP levels, membrane potentials, and activities of mitochondrial complexes I, II, and V and dehydrogenases that had been decreased by acrolein exposure. LM reduced acrolein-induced oxidant generation, calcium levels, protein oxidation, and DNA damage to a greater degree than LA. And, total antioxidant capacity, glutathione content, glutathione S-transferase, and superoxide dismutase activities and expression of nuclear factor-E2-related factor 2 were increased by LM relative to LA. These results suggest that LM is a more potent mitochondrial-protective agent and antioxidant than LA in protecting RPE from oxidative damage.
α-硫辛酸（LA）作为一种预防和治疗与线粒体功能氧化破坏相关的各种疾病的药物，已得到广泛研究。为了研究一种相关的线粒体抗氧化剂，我们比较了硫辛酰胺（LM，LA的中性酰胺）与LA对人视网膜色素上皮（RPE）细胞系氧化损伤和线粒体功能障碍的影响。丙烯醛是香烟烟雾的主要成分和脂质过氧化的产物，用于诱导RPE细胞中的线粒体氧化损伤。总体而言，在使用可比浓度时，LM在预防丙烯醛诱导的线粒体功能障碍和氧化应激方面比LA更有效。相对于LA，LM提高了ATP水平、膜电位以及线粒体复合物I、II和V以及因丙烯醛暴露而降低的脱氢酶的活性。LM比LA更大程度地降低了丙烯醛诱导的氧化剂生成、钙水平、蛋白质氧化和DNA损伤。并且，相对于LA，LM增加了总抗氧化能力、谷胱甘肽含量、谷胱甘肽S-转移酶和超氧化物歧化酶活性以及核因子E2相关因子2的表达。这些结果表明，在保护RPE免受氧化损伤方面，LM是一种比LA更有效的线粒体保护剂和抗氧化剂。
