Esparza José L, Gómez Mercedes, Rosa Nogués M, Paternain José L, Mallol Jordi, Domingo José L
Laboratory of Toxicology and Environmental Health, School of Medicine, Rovira i Virgili University, Reus, Spain.
J Pineal Res. 2005 Sep;39(2):129-36. doi: 10.1111/j.1600-079X.2005.00225.x.
The pro-oxidant activity of aluminum (Al), the protective role of exogenous melatonin, as well as the mRNA levels of some antioxidant enzymes, were determined in cortex and cerebellum of rats following exposure to Al and/or melatonin. Two groups of male rats received intraperitoneal injections of Al lactate or melatonin at doses of 7 mg Al/kg/day and 10 mg/kg/day, respectively, for 11 wk. A third group of animals received concurrently Al lactate (7 mg Al/kg/day) plus melatonin (10 mg/kg/day) during the same period. A fourth group of rats was used as control. At the end of the treatment, the cerebral cortex and cerebellum were removed and processed to examine the following oxidative stress markers: glutathione transferase (GST), reduced glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD), glutathione reductase, glutathione peroxidase (GPx), catalase (CAT), thiobarbituric acid reactive substances (TBARS), as well as protein content. Moreover, gene expression of Cu-ZnSOD, MnSOD, GPx and CAT was evaluated by real-time RT-PCR. On the other hand, Al, Fe, Mn, Cu and Zn concentrations were determined in cortex and cerebellum of rats. Oxidative stress was promoted in both neural regions following Al administration, resulting from the pro-oxidant activity related with an increase in tissue Al concentrations. In contrast, melatonin exerted an antioxidant action which was related with an increase in the mRNA levels of the antioxidant enzymes evaluated. The results of the present investigation emphasize the potential use of melatonin as a supplement in the therapy of neurological disorders in which oxidative stress is involved.
在大鼠暴露于铝（Al）和/或褪黑素后，测定了铝的促氧化活性、外源性褪黑素的保护作用以及一些抗氧化酶的mRNA水平。两组雄性大鼠分别以7mg铝/千克/天和10mg/千克/天的剂量腹腔注射乳酸铝或褪黑素，持续11周。第三组动物在同一时期同时接受乳酸铝（7mg铝/千克/天）加褪黑素（10mg/千克/天）。第四组大鼠用作对照。治疗结束时，取出大脑皮层和小脑并进行处理，以检测以下氧化应激标志物：谷胱甘肽转移酶（GST）、还原型谷胱甘肽（GSH）、氧化型谷胱甘肽（GSSG）、超氧化物歧化酶（SOD）、谷胱甘肽还原酶、谷胱甘肽过氧化物酶（GPx）、过氧化氢酶（CAT）、硫代巴比妥酸反应性物质（TBARS）以及蛋白质含量。此外，通过实时RT-PCR评估铜锌超氧化物歧化酶、锰超氧化物歧化酶、谷胱甘肽过氧化物酶和过氧化氢酶的基因表达。另一方面，测定了大鼠大脑皮层和小脑中铝、铁、锰、铜和锌的浓度。铝给药后，两个神经区域均出现氧化应激增强，这是由与组织铝浓度增加相关的促氧化活性引起的。相比之下，褪黑素发挥了抗氧化作用，这与所评估的抗氧化酶的mRNA水平增加有关。本研究结果强调了褪黑素作为一种补充剂在治疗涉及氧化应激的神经疾病中的潜在用途。
