Lithium plus pilocarpine induced status epilepticus - biochemical changes

Lithium plus pilocarpine induced status epilepticus - biochemical changes
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DOI:
10.1016/s0168-0102(99)00120-0
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发表时间:
2000-02-01
影响因子:
2.9
通讯作者:
Simonic, A
Simonic, A
中科院分区:
医学4区
文献类型:
--
作者:
Erakovic, V;Zupan, G;Simonic, A

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本研究的目的是探讨锂加匹罗卡品治疗中促进细胞损伤的生化机制的变化以及由此导致的癫痫持续状态。测定了汉诺威-Wistar大鼠全脑游离脂肪酸(FFA)水平,以及额叶、小脑、脑桥-延髓等脑区超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPX)、谷氨酸脱氢酶(Glu脱氢酶)、天冬氨酸转氨酶(AST)、丙氨酸转氨酶(AST)、γ-谷氨酰转移酶、碱性磷酸酶(ALP)、乳酸脱氢酶(LDH)和肌酸激酶(CK)的活性。对照组是完好无损的,没有既往实验史。氯化锂(125 mg/kg ip)在匹罗卡品(30 mg/kg)注射前20h注射。给药后1~2 1/2 h处死大鼠。结果表明,锂与匹罗卡品合用及致痫持续状态使大鼠脑内游离脂肪酸含量显著增加。治疗组大鼠额叶皮质、小脑和海马区GPx活性降低,但未见超氧化物歧化酶活性降低。癫痫持续状态大鼠额叶皮质AST和LDH活性升高,额叶皮质和桥脑-延髓区可溶性ALP活性升高,海马膜结合型ALP活性升高。在被检查的大脑区域中,其他被分析的酶的活性没有变化。目前的数据表明,锂加匹罗卡品治疗引起的生化变化存在明显的地区差异,由此导致的癫痫持续状态,额叶皮质所带来的影响最大。(C)2000爱思唯尔爱尔兰科学有限公司。保留所有权利。
The aim of the study was to investigate the changes in biochemical mechanisms facilitating cellular damages in the lithium plus pilocarpine treatment and the resulting status epilepticus. The whole brain free fatty acid (FFA) level as well as the activities of superoxide dismutase (SOD), glutathione peroxidase (GPX), glutamate dehydrogenase, aspartate-aminotransferase (AST), alanine-aminotransferase, gamma-glutamoyl transferase, alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and creatine kinase in the frontal cortex, cerebellum hippocampus and pons-medulla region of Hannover-Wistar rats were determined. The control group was intact with no previous experimental history. LiCl (125 mg/kg i.p.) was injected 20 h prior to pilocarpine (30 mg/kg i.p.) and the treated rats were sacrificed 1 or 2 1/2 h after pilocarpine administration. The results show that lithium plus pilocarpine administration and the resulting status epilepticus produced the significant increase of the brain FFA content. Decreased GPX activities were detected in the frontal cortex, cerebellum and hippocampus of the treated rats without the accompanying decrease of SOD activity. Increased AST and LDH activities were observed in the frontal cortex, increased soluble ALP activities in the frontal cortex and pons-medulla region whereas the increased activity of membrane bound ALP was detected in the hippocampus of the rats with status epilepticus. Activities of the other analysed enzymes did not change in the examined brain regions. The presented data indicate clear regional differences of biochemical changes caused by lithium plus pilocarpine treatment and the resulting status epilepticus, frontal cortex bring the most affected site. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.