2,3-Butanedione, 2,4-Pentanedioneおよび2,5-Hexanedioneの末梢神経毒性に関する電気生理学的研究

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A series of studies was made to clarify the relationship of the chemical structures of 2,3-butanedione (2,3-BDione), 2,4-pentanedione (2,4-PDione) and 2,5-hexanedione (2,5-HDione) to neurotoxicity in terms of n-hexane neuropathy and relative neurotoxic potentials, using electrophysiological methods. These compounds are all molecularly symmetrical diketones with 4,5 and 6 carbons respectively. A 200 mg/kg dose of each compound was administered subcutaneously five days a week to one of three groups of eight rats. This program continued for 40 weeks in the case of 2,3-BDione and 2,4-PDione and for 14 weeks in the case of 2,5-HDione. Electrophysiological studies of the effects of the compounds on the peripheral nerve were performed by measuring maximum motor conduction velocities (MCV) and sensory conduction velocities (SCV) in the tail nerve of the rats. Residual latencies (RL), motor distal latencies (DL), amplitudes of the muscle action potentials (MAP), and amplitudes of the nerve action potentials (NAP) were also estimated. A significant slowing of MCV began to be observed in the 2,5-HDione group at the 6th week and in the 2,4-PDione group at 10th week. At 8th week, a significant decrease in SCV was also observed in these two groups. The degree of reduction in both MCV and SCV was more pronounced in the 2,5-HDione group than in the 2,4-PDione group. In the 2,5-HDione group, the MCV values were more strongly affected than the SCV values. On the other hand, in the 2,4-PDione group the SCV values were slowed more than the MCV values. The amplitudes of MAP and NAP in the 2,5-HDione group decreased significantly at 12th week and at 10th week, respectively. In the 2,4-PDione group, a significant decrease in NAP amplitudes was observed at 16th week and that in MAP amplitudes at 28th week. The 2,3-BDione group showed a decrease in MAP amplitudes at 28th week. The RL and DL were markedly prolonged at an early stage only in the 2,5-HDione group. The γ-diketone of 6,7 and 8 normal chains of the aliphatic hydrocarbons has been reported to cause peripheral distal axonopathy with giant axonal degeneration. This disorder is named γ-diketone neuropathy. In this study, neurotoxic evidence was revealed by 2,4-PDione, which is 5-carbon and symmetrical β-diketone. However, between the 2,4-PDione group and the 2,5-HDione group, some differences exist in clinical and electrophysiological features, suggesting that the mechanisms of neurotoxic action in these two compounds may differ. The compound 2,3-BDione gave no other peripheral neurological findings than a temporal decrease in MAP amplitudes, and therefore may be considered to be non-neurotoxic.
社団法人日本産業衛生学会の論文
1983-11-20

2,3-Butanedione, 2,4-Pentanedioneおよび2,5-Hexanedioneの末梢神経毒性に関する電気生理学的研究

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