The spatio-temporal pattern of the axonopathy associated with the neurotoxicity of 3,4-dimethyl-2,5-hexanedione in the rat.
J Neuropathol Exp Neurol
; 42(5): 548-60, 1983 Sep.
Article
em En
| MEDLINE
| ID: mdl-6310058
ABSTRACT
The neurotoxicity of the gamma-diketone 3,4-dimethyl-2,5-hexanedione(DMHD) was studied to determine the distribution of the neuropathologic changes and the temporal sequence during the intoxication period and following five and 15 weeks of recovery. Intoxication with 3,4-dimethyl-2,5-hexanedione at a daily dose of 0.25 mmoles/kg led to a profound clinical neuropathy, resulting in paralysis of all four limbs after 12-15 days. The cumulative toxic dose for this gamma-diketone was 3-4 mmoles/kg, indicating that dimethyl substitution increased the neurotoxicity of gamma-diketones by a factor of 20-30. The neuropathy was characterized histologically by giant axonal swellings in the proximal axon of the lower motor neuron in a distribution similar to IDPN (beta,beta'-iminodipropionitrile)-neuropathy, with swellings in the anterior horn, intraspinal anterior root, and the proximal anterior root. These swellings developed from six to 12 days of intoxication and were still evident after 15 weeks of recovery. The fact that dimethyl substitution of 2,5-hexanedione accelerated the neuropathy and was characterized by proximal axonal swellings has two important implications 1) that formation of pyrrole derivatives may be an important step in the pathogenesis of gamma-diketone neuropathies, and 2) that the neurofilament neuropathies may represent a continuum of toxic neuropathies in which the rate of action of the neurotoxin ultimately determines the proximo-distal location of the axonal swellings.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Axônios
/
Doenças do Sistema Nervoso Periférico
/
Hexanonas
/
Cetonas
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
J Neuropathol Exp Neurol
Ano de publicação:
1983
Tipo de documento:
Article