Graham D G, Amarnath V, Valentine W M, Pyle S J, Anthony D C
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
Crit Rev Toxicol. 1995;25(2):91-112. doi: 10.3109/10408449509021609.
Two commonly employed solvents, n-hexane and carbon disulfide (CS2), although chemically dissimilar, result in identical neurofilament-filled swellings of the distal axon in both the central and peripheral nervous systems. Whereas CS2 is itself a neurotoxicant, hexane requires metabolism to the gamma-diketone, 2,5-hexanedione (HD). Both HD and CS2 react with protein amino functions to yield initial adducts (pyrrolyl or dithiocarbamate derivatives, respectively), which then undergo oxidation or decomposition to an electrophile (oxidized pyrrole ring or isothiocyanate), that then reacts with protein nucleophiles to result in protein cross-linking. It is postulated that progressive cross-linking of the stable neurofilament during its anterograde transport in the longest axons ultimately results in the accumulation of neurofilaments within axonal swellings. Reaction with additional targets appears to be responsible for the degeneration of the axon distal to the swellings.
两种常用溶剂，正己烷和二硫化碳（CS2），尽管化学性质不同，但在中枢和外周神经系统中都会导致远端轴突出现相同的充满神经丝的肿胀。虽然CS2本身就是一种神经毒物，但己烷需要代谢为γ-二酮，即2,5-己二酮（HD）。HD和CS2都与蛋白质氨基功能发生反应，分别产生初始加合物（吡咯基或二硫代氨基甲酸盐衍生物），然后这些加合物经历氧化或分解形成亲电试剂（氧化的吡咯环或异硫氰酸酯），该亲电试剂再与蛋白质亲核试剂反应导致蛋白质交联。据推测，在最长轴突中神经丝顺向运输过程中，稳定的神经丝逐渐交联最终导致轴突肿胀内神经丝的积累。与其他靶点的反应似乎是导致肿胀远端轴突变性的原因。
