School of Public Health, Anhui Medical University, Meishan road 81, Hefei, Anhui, China.
Brain Res. 2010 Apr 9;1324:96-102. doi: 10.1016/j.brainres.2010.02.024. Epub 2010 Feb 12.
Aluminum (Al) is among the most abundant elements on earth, it has been associated with the etiology of Alzheimer's disease. In the present study, AlCl(3) was administered with the dose of 10, 50 or 300 mg/kg b.wt/day through diet for 100 days. On day 101, overnight-fasted animals were sacrificed, the whole brains were removed and the cells from hippocampus or cortex were separated for the measurements: malondialdehyde (MDA), superoxide dismutase (SOD), nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) damage. AlCl(3) exposure resulted in increased MDA levels accompanied by decreased activities of SOD in the cells. Comet assay demonstrated that aluminum induces nDNA damage in a dose-dependent manner, dramatically increased formation of 8-hydroxy 2-deoxyguanosine (8-OHdG) in the mtDNA isolated from the cells was also measured. The alterations seem more serious than the results displayed by the studies performed with lower doses of aluminum. However, a detailed biochemical mechanism by which aluminum accelerates mtDNA damage has not yet been identified, but the decrease in superoxide dismutase (SOD) activity and increase in MDA level in aluminum-treated mice may suggest the involvement of oxidative stress.
铝(Al)是地球上最丰富的元素之一,它与阿尔茨海默病的病因有关。在本研究中,通过饮食给予 AlCl(3),剂量为 10、50 或 300mg/kg bw/天,共 100 天。在第 101 天,禁食过夜的动物被处死,取出整个大脑,分离海马或皮质细胞,用于测量:丙二醛(MDA)、超氧化物歧化酶(SOD)、核 DNA(nDNA)和线粒体 DNA(mtDNA)损伤。铝暴露导致 MDA 水平升高,同时 SOD 活性降低。彗星试验表明,铝以剂量依赖的方式诱导 nDNA 损伤,还测量了从细胞中分离出的 mtDNA 中 8-羟基 2-脱氧鸟苷(8-OHdG)形成量的显著增加。与用较低剂量铝进行的研究相比,这些变化似乎更为严重。然而,铝加速 mtDNA 损伤的详细生化机制尚未确定,但铝处理小鼠中超氧化物歧化酶(SOD)活性降低和 MDA 水平升高可能表明氧化应激的参与。