Semprine Jimena, Ferrarotti Nidia, Musacco-Sebio Rosario, Saporito-Magriñá Christian, Fuda Julián, Torti Horacio, Castro-Parodi Mauricio, Damiano Alicia, Boveris Alberto, Repetto Marisa G
Department of General and Inorganic Chemistry, University of Buenos Aires, Buenos Aires, Argentina.
Metallomics. 2014 Nov;6(11):2083-9. doi: 10.1039/c4mt00159a.
Dose- and time-dependent antioxidant responses to Fe (0-60 mg kg(-1)) and Cu overloads (0-30 mg kg(-1)) in rat brains are described by the C50 and the t1/2, the brain metal concentration and the time for half maximal oxidative responses. Brain GSH and the GSH/GSSG ratio markedly decreased after Fe and Cu treatments (50-80%) with a t1/2 of 9-10 h for GSH and of 4 h for GSH/GSSG for both metals. The GSH/GSSG ratio was the most sensitive indicator of brain oxidative stress. The decrease of GSH and the increase of in vivo chemiluminescence had similar time courses. The C50 for brain chemiluminescence, GSH and hydrophilic and lipophilic antioxidants were in similar ranges (32-36 μg Fe g(-1) brain and 10-18 μg Cu g(-1) brain), which indicated a unique free-radical mediated process for each metal. The brain concentration of hydrophilic and lipophilic antioxidants decreased after Fe and Cu loads; hydrophilic antioxidants decreased by 46-68% with a t1/2 of 10-11 h and lipophilic antioxidants decreased by 75-45% with a t1/2 of 10-12 h. Cu,Zn-SOD and CAT activities and the protein expression were adaptively increased (100-90% after Fe and Cu loads), with a t1/2 of 8-12 h. GPx-4 activity decreased after both metal loads by 73-27% with a t1/2 of 8-4 h with decreased protein expression.
通过半数效应浓度（C50）和半衰期（t1/2）、脑金属浓度以及达到半数最大氧化反应的时间，描述了大鼠脑对铁（0 - 60毫克/千克）和铜过载（0 - 30毫克/千克）的剂量和时间依赖性抗氧化反应。铁和铜处理后，脑内谷胱甘肽（GSH）和GSH/GSSG比值显著降低（50 - 80%），两种金属处理下GSH的t1/2为9 - 10小时，GSH/GSSG的t1/2为4小时。GSH/GSSG比值是脑氧化应激最敏感的指标。GSH的降低和体内化学发光的增加具有相似的时间进程。脑化学发光、GSH以及亲水性和脂溶性抗氧化剂的C50在相似范围内（脑内32 - 36微克铁/克和10 - 18微克铜/克），这表明每种金属都有独特的自由基介导过程。铁和铜负荷后，脑内亲水性和脂溶性抗氧化剂浓度降低；亲水性抗氧化剂降低46 - 68%，t1/2为10 - 11小时，脂溶性抗氧化剂降低75 - 45%，t1/2为10 - 12小时。铜锌超氧化物歧化酶（Cu,Zn - SOD）和过氧化氢酶（CAT）活性及蛋白表达适应性增加（铁和铜负荷后增加100 - 90%），t1/2为8 - 12小时。两种金属负荷后，谷胱甘肽过氧化物酶4（GPx - 4）活性降低73 - 27%，t1/2为8 - 4小时，蛋白表达也降低。
