Palaniappan A R, Dai A
Department of Biochemistry, Yokohama City University, Maioka-cho 641-12, Yokohama 244-0813, Japan.
Neurochem Res. 2007 Sep;32(9):1552-8. doi: 10.1007/s11064-007-9355-4. Epub 2007 May 3.
Oxidative damage has been implicated to be a major causative factor in the decline in physiological functions that occur during the ageing process. Mitochondria are known to be a rich source for the production of free radicals and, consequently, mitochondrial components are susceptible to lipid peroxidation (LPO) that decreases respiratory activity. In the present investigation, we have evaluated mitochondrial LPO, 8-oxo-dG, oxidized glutathione, reduced glutathione, ATP, lipoic acid, TCA cycle enzymes and electron transport chain (ETC) complex activities in the brain of young versus aged rats. In aged rats, the contents of LPO, oxidized glutathione and 8-oxo-dG were high whereas reduced glutathione, ATP, lipoic acid, TCA cycle enzymes and ETC complex activities were found to be low. Lipoic acid administration to aged rats reduced the levels of mitochondrial LPO, 8-oxo-dG and oxidized glutathione and enhanced reduced glutathione, ATP, lipoic acid and ETC complex activities. In young rats lipoic acid administration showed only minimal lowering the levels of LPO, 8-oxo-dG and oxidized glutathione and slight increase in the levels of reduced glutathione, ATP, lipoic acid, TCA cycle enzymes and ETC complex activities. These findings suggest that the dithiol, lipoic acid, provides protection against age-related oxidative damage in the mitochondria of aged rats.
氧化损伤被认为是衰老过程中生理功能衰退的一个主要致病因素。已知线粒体是自由基产生的丰富来源，因此，线粒体成分易受脂质过氧化（LPO）影响，而脂质过氧化会降低呼吸活性。在本研究中，我们评估了年轻大鼠与老年大鼠大脑中线粒体LPO、8-氧代脱氧鸟苷（8-oxo-dG）、氧化型谷胱甘肽、还原型谷胱甘肽、三磷酸腺苷（ATP）、硫辛酸、三羧酸循环（TCA）酶和电子传递链（ETC）复合物的活性。在老年大鼠中，LPO、氧化型谷胱甘肽和8-oxo-dG的含量较高，而还原型谷胱甘肽、ATP、硫辛酸、TCA循环酶和ETC复合物的活性较低。给老年大鼠施用硫辛酸可降低线粒体LPO、8-oxo-dG和氧化型谷胱甘肽的水平，并提高还原型谷胱甘肽、ATP、硫辛酸和ETC复合物的活性。在年轻大鼠中，施用硫辛酸仅使LPO、8-oxo-dG和氧化型谷胱甘肽的水平略有降低，而还原型谷胱甘肽、ATP、硫辛酸、TCA循环酶和ETC复合物的活性略有增加。这些发现表明，二硫醇硫辛酸可保护老年大鼠线粒体免受与年龄相关的氧化损伤。
