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神经毒性伴随神经细胞凋亡的过程。本实验假设在化学物质的作用下，活性氧能诱导神经元凋亡，所用的化学物质为2，5-己二酮和顺铂。2，5-己二酮是已知的神经毒性物质，它是正己烷和甲基正丁基酮的代谢产物。它影响轴突，其病理学是众所周知的轴突肿胀充满神经丝。顺铂被用作抗癌药物，其神经毒性是特异性的感觉神经。所用材料为原代培养的神经元，其被认为具有更多的体内特性。结果表明：（1）2，5-己二酮可引起小鼠背根神经节细胞DNA的断裂。(2)顺铂诱导小鼠背根神经节神经元DNA断裂。(3)2，5-己二酮不直接作用于DNA链，也不诱发活性氧自由基。（4）顺铂不直接作用于DNA链，也不诱发活性氧自由基。2，5-己二酮诱导的细胞凋亡可得到梯状条带，但水平较弱，有待进一步放大。抗氧化物质保护顺铂引起的神经细胞死亡，但不能检测到活性氧。

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.