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氧化应激在二苯基二硒诱导的幼鼠癫痫发作中的作用。

Involvement of oxidative stress in seizures induced by diphenyl diselenide in rat pups.

作者信息

Prigol Marina, Wilhelm Ethel A, Schneider Caroline C, Rocha Joao B T, Nogueira Cristina W, Zeni Gilson

机构信息

Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil.

出版信息

Brain Res. 2007 May 25;1147:226-32. doi: 10.1016/j.brainres.2007.01.126. Epub 2007 Feb 4.

Abstract

In the present study the potential neurotoxicity of diphenyl diselenide, as measured by the manifestation of seizures in rat pups (postnatal days, PND, 12-14) was evaluated. The results suggest that the latency for the appearance of tonic-clonic seizures, characterized by rearing and falling of rat pups body, was dependent of the dose tested. Diphenyl diselenide at high doses induced seizure episodes in rat pups. The highest dose of diphenyl diselenide (500 mg/kg) increased the levels of lipid peroxidation and catalase activity as well as decreased delta-ALA-D (delta-aminolevulinate dehydratase) and Na(+), K(+) ATPase activity in the brain of rat pups. Our results indicate the possible involvement of free radical oxygen injury in diphenyl diselenide-induced seizures. The data obtained with the dose of 150 mg/kg in the brain of rats that exhibited seizures are: an increase in lipid peroxidation levels; the lack of effect on catalase activity; an inhibition of delta-ALA-D activity, supporting that the enzyme activity is more sensitive than other parameters analyzed as an indicator of oxidative stress. The lowest dose of diphenyl diselenide emphasizes the relationship between the appearance of seizures and the latency for the onset of the first episode. Taken together, this paper could add to our understanding of diphenyl diselenide neurotoxic effect demonstrated by the appearance of seizures which are, at least in part, related to the oxidative stress.

摘要

在本研究中,通过观察新生大鼠(出生后第12 - 14天)的癫痫发作表现,评估了二苯基二硒醚的潜在神经毒性。结果表明,以大鼠幼崽身体直立和跌倒为特征的强直阵挛性癫痫发作的潜伏期,取决于所测试的剂量。高剂量的二苯基二硒醚可诱发大鼠幼崽癫痫发作。二苯基二硒醚的最高剂量(500 mg/kg)可增加脂质过氧化水平和过氧化氢酶活性,同时降低大鼠幼崽脑中的δ-氨基乙酰丙酸脱水酶(delta-ALA-D)和钠钾ATP酶活性。我们的结果表明,自由基氧损伤可能参与了二苯基二硒醚诱发的癫痫发作。在出现癫痫发作的大鼠脑中,150 mg/kg剂量所获得的数据如下:脂质过氧化水平升高;对过氧化氢酶活性无影响;δ-氨基乙酰丙酸脱水酶活性受到抑制,这支持了该酶活性作为氧化应激指标比其他分析参数更敏感。二苯基二硒醚的最低剂量强调了癫痫发作的出现与首次发作潜伏期之间的关系。综上所述,本文有助于我们理解二苯基二硒醚的神经毒性作用,这种作用通过癫痫发作表现出来,且至少部分与氧化应激有关。

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