In Vivo Evaluation of Hippocampal Anti-Oxidant Ability of Zonisamide in Rats
In Vivo Evaluation of Hippocampal Anti-Oxidant Ability of Zonisamide in Rats
复制标题
唑尼沙胺大鼠海马抗氧化能力的体内评价
作者：
J. Tokumaru;Y. Ueda;H. Yokoyama;A. Nakajima;Taku Doi;Y. Mitsuyama;H. Ohya‐Nishiguchi;H. Kamada
采用在体微透析技术研究唑尼沙胺（ZNS）对2种外源性氮氧自由基（3-氨甲酰基-2，2，5，5-四甲基吡咯烷-1-氧自由基（3-aminoyl-PROXYL）和3-甲氧羰基-2，2，5，5-四甲基吡咯烷-1-氧自由基（3-methoxycarbonyl-2，2，5，5-tetramethylpyrrolidine-1-oxyl，PCAM）的抗氧化作用。这些外源性氮氧自由基的信号强度的时间依赖性变化，从海马灌流液中观察到使用X波段ESR光谱仪在20分钟的时间间隔。氮氧自由基的ESR信号强度在所有动物中均呈指数下降，这表明其半衰期可用作估计氮氧自由基衰减速率的参数。氮氧自由基在生物系统中暴露于还原剂时失去其顺磁性。因此，半衰期反映了体内还原能力。虽然不能通过血脑屏障（BBB）的氨甲酰-PROXYL的半衰期与对照组相比没有变化，但ZNS预处理显著缩短了可以通过BBB的PCAM的半衰期。这些结果表明，ZNS诱导的还原能力的增加并没有发生在细胞外空间，而是主要在神经细胞膜。本研究是ZNS在自由活动动物中还原能力的首次体内评价。
We evaluated the anti-oxidant property of zonisamide (ZNS) in the rat brain under freely moving conditions by means of in vivo microdialysis of two exogenous nitroxide radicals, 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (carbamoyl-PROXYL) and 3-methoxy carbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (PCAM). Time-dependent changes in the signal intensities of these exogenous nitroxide radicals obtained from the hippocampal perfusates were observed using an X-band ESR spectrometer at 20-min intervals. The ESR signal intensities of nitroxide radicals decreased exponentially in all animals, which indicates that their half-life could be used as a parameter to estimate the decay rate of nitroxide radicals. Nitroxide radicals lose their paramagnetism when exposed to reductants in a biological system. Thus, half-life reflects the in vivo reducing ability. Although the half-life of carbamoyl-PROXYL, which could not pass the blood-brain barrier (BBB), was not changed when compared with the controls, pre-treatment with ZNS significantly shortened the half-life of PCAM, which could pass through the BBB. These findings suggest that the ZNS-induced increase in reducing ability did not occur within the extracellular space, but rather mainly at the neural cell membrane. This study is the first in vivo evaluation of the reducing ability of ZNS in freely moving animals.