Industrial chemicals induced neural apoptosis with its relation to active oxygen species

本研究的目的是探讨工业化学品的神经毒性与神经细胞凋亡的关系。我们的假设是，在化学攻击下，神经元会被活性氧物种诱导凋亡。我们使用的化学物质是2，5-己二酮和顺铂。2，5-己二酮是已知的神经毒性物质，是正己烷和甲基正丁基酮的代谢物。它影响轴突，其病理是众所周知的轴突肿胀充满神经细丝。顺铂被用作抗癌药物，其神经毒性是针对感觉神经的。所用材料为原代培养的神经元，被认为是具有更多体内特性的材料。结果如下：(1)2，5-己二酮诱导小鼠背根神经节细胞DNA断裂；(2)顺铂诱导小鼠背根神经节神经元DNA断裂；(3)2，5-己二酮不直接影响DNA链，也不诱导氧自由基。(4)顺铂不直接影响DNA链，也不诱导氧自由基。我们从2，5-己二酮诱导的细胞凋亡中获得了阶梯，但水平很低，需要进一步扩增。抗氧化剂保护顺铂诱导的神经细胞死亡，但不能检测到活性氧物种本身。

Aim of our study is to investigate the process relating to neurotoxicity of industrial chemicals accompanied by neuronal apoptosis. The hypothesis we are based on is that under the chemical assault apoptosis of neurons will be induced by active oxygen species.Chemical substances we used were 2,5-hexanedione and cisplatin. 2,5-Hexanedione is well known neurotoxic substance which is a metabolite of n-hexane and methyl n-butyle ketone. It affects axons and its pathology is well-known by axonal swelling filled with neurofilaments. Cisplatin is used as anti-cancer drug and its neurotoxicity is specific to sensory nerves. Material used were Primary culture neurons were used as materials which is believed to have more in vivo characters. Also single strand DNA was used to measure the direct effect of the chemicals to DNA.The results were as follows ;(1) 2,5-Hexanedione induced fragmentation of DNA in mouse dorsal root ganglion neurons.(2) Cisplatin induced fragmentation of DNA in mouse dorsal root ganglion neurons.(3) 2,5-Hexanedione did not directly affect DNA strands nor induced active oxygen radicals(4) Cisplatine did not directly affect DNA strands nor induced active oxygen radicalsTo study further, we tried to detect DNA ladder in cultured cell. We got the ladder from 2,5-hexanedione induced apoptosis but the level was very week and needs further amplification. Antioxidant substances protected neuronal cell death by cisplatin but could not detect active oxygen species itself.