Chang M L, Klaidman L, Adams J D
Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Los Angeles, USA.
Mol Chem Neuropathol. 1995 Oct;26(2):95-106. doi: 10.1007/BF02815008.
Intracerebroventricular t-butyl hydroperoxide has been reported to induce damage to many types of brain cells. t-Butyl hydroperoxide administration increases glutathione disulfide levels and decreases levels of glutathione. Young adult mice may be more protected from t-butyl hydroperoxide than mature mice due to their higher glutathione levels, even after the administration of t-butyl hydroperoxide. This leads to our current study, investigating glutathione peroxidase and glutathione disulfide reductase in 2-mo-old and 8-mo-old mice. Furthermore, malondialdehyde levels were measured with the thiobarbituric acid assay and compared between the two age groups. Mature mice detoxify glutathione disulfide less readily than young adult mice. Glutathione disulfide reductase activity increases in young adult mice after t-butyl hydroperoxide administration, but not in mature mice. Glutathione peroxidase activity is significantly lower in 8-mo-old than 2-mo-old mouse striatum after t-butyl hydroperoxide administration. Furthermore, malondialdehyde levels in the 8-mo-old striatum increase significantly 20 min after t-butyl hydroperoxide administration. This suggests that age plays a factor in protective mechanisms that are involved in oxidative stress in the brain.
据报道，脑室内注射叔丁基过氧化氢会对多种类型的脑细胞造成损伤。给予叔丁基过氧化氢会增加谷胱甘肽二硫化物水平并降低谷胱甘肽水平。即使在给予叔丁基过氧化氢后，年轻成年小鼠由于其较高的谷胱甘肽水平，可能比成熟小鼠更能抵御叔丁基过氧化氢的损伤。这引发了我们当前的研究，即对2月龄和8月龄小鼠的谷胱甘肽过氧化物酶和谷胱甘肽二硫化物还原酶进行研究。此外，用硫代巴比妥酸法测定丙二醛水平，并在两个年龄组之间进行比较。成熟小鼠比年轻成年小鼠更难解毒谷胱甘肽二硫化物。给予叔丁基过氧化氢后，年轻成年小鼠的谷胱甘肽二硫化物还原酶活性增加，但成熟小鼠没有。给予叔丁基过氧化氢后，8月龄小鼠纹状体中的谷胱甘肽过氧化物酶活性显著低于2月龄小鼠。此外，给予叔丁基过氧化氢20分钟后，8月龄纹状体中的丙二醛水平显著升高。这表明年龄在大脑氧化应激相关的保护机制中起作用。
