Differential effects of antipsychotics on expression of antioxidant enzymes and membrane lipid peroxidation in rat brain
Differential effects of antipsychotics on expression of antioxidant enzymes and membrane lipid peroxidation in rat brain
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DOI：
10.1016/s0022-3956(02)00048-1
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发表时间：
2003-01-01
影响因子：
4.8
通讯作者：
Mahadik, SP
中科院分区：
文献类型：
--
作者：
Parikh, V;Khan, MM;Mahadik, SP
典型和非典型抗精神病药物在神经递质受体亲和力谱，以及它们在精神分裂症患者中的疗效和副作用方面存在显著差异。已发现典型的抗精神病药物增加大鼠中的氧化（即自由基介导的）细胞损伤。由于精神分裂症也涉及氧化损伤，因此了解这些抗精神病药物对抗氧化酶表达和氧化损伤的不同影响可能非常重要。比较了氟哌啶醇（HAL）（一种典型的抗精神病药）慢性暴露与利培酮（RIS）或氯氮平（CLZ）或奥氮平（OLZ）（非典型抗精神病药）对大鼠脑中抗氧化防御酶和脂质过氧化作用的影响。抗氧化酶和羟烯醛（HAE）的水平进行了测量，在大鼠脑细胞液和脂肪酸测定脑细胞膜。慢性HAL治疗45和90天显着降低锰超氧化物歧化酶（MnSOD），铜锌超氧化物歧化酶（CuZnSOD）和过氧化氢酶（CAT）的活性与平行显着增加（HAE），在大鼠脑中的脂质过氧化反应的标志物。酶活性的水平与酶蛋白的水平非常好地相关，表明变化可能是在净蛋白的表达。然而，RIS、CLZ和OLZ处理在45天和90天后都没有产生抗氧化酶和HAE水平的任何改变。有没有改变的饱和以及多不饱和脂肪酸在脑细胞膜的水平。这些研究结果表明，长期管理的HAL，但没有研究的药物诱导氧化应激的抗氧化酶的水平的持续变化，并导致膜脂质过氧化。(C)2002爱思唯尔科技有限公司。保留所有权利。
Typical and atypical antipsychotics significantly differ in their neurotransmitter receptor affinity profiles, and their efficacy and side effects in schizophrenic patients. Typical antipsychotics have been found to increase the oxidative (i.e. free radical-mediated) cellular injury in rats. Since schizophrenia also involves oxidative injury, the understanding of differential effects of these antipsychotics oil expression of antioxidant enzymes and oxidative injury may be very critical. The effect of chronic exposure of haloperidol (HAL), a typical antipsychotic, was compared to effects of risperidone (RIS) or clozapine (CLZ) or olanzapine (OLZ), atypical antipsychotics on antioxidant defense enzymes and lipid peroxidation in the rat brain. The levels of antioxidant enzymes and hydroxyalkenals (HAEs) were measured in rat brain cytosol and fatty acids were measured in brain cell membranes. Chronic HAL treatment for both 45 and 90 days significantly decreased manganese-superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD) and catalase (CAT) activity with parallel marked increase in (HAEs), a marker of lipid peroxidation in rat brain. The levels of enzymatic activity very well correlated with the levels of enzyme proteins indicating that the changes were probably in the expression of net protein. However, RIS, CLZ and OLZ treatments did not produce any alterations in the levels of antioxidant enzymes and HAEs, both after 45 and 90 days. There were no alterations in the levels of saturated as well as polyunsaturated fatty acids in brain membranes. These findings indicate that chronic administration of HAL, but none of the studied atypicals induce oxidative stress by persistent changes in the levels of antioxidant enzymes and cause membrane lipid peroxidation. (C) 2002 Elsevier Science Ltd. All rights reserved.