Peripheral neuropathy in rats exposed to dichloroacetate.
J Neuropathol Exp Neurol
; 68(9): 985-93, 2009 Sep.
Article
em En
| MEDLINE
| ID: mdl-19680144
ABSTRACT
The use of dichloroacetate (DCA) for treating patients with mitochondrial diseases is limited by the induction of peripheral neuropathy. The mechanisms of DCA-induced neuropathy are not known. Oral DCA treatment (50-500 mg/kg per day for up to 16 weeks) induced tactile allodynia in both juvenile and adult rats; concurrent thermal hypoalgesia developed at higher doses. Both juvenile and adult rats treated with DCA developed nerve conduction slowing that was more pronounced in adult rats. No overt axonal or glial cell abnormalities were identified in peripheral nerves or spinal cord of any DCA-treated rat, but morphometric analysis identified a reduction of mean axonal caliber of peripheral nerve myelinated fibers. Dichloroacetate treatment also caused accumulation of oxidative stress markers in the nerves. These data indicate that behavioral, functional, and structural indices of peripheral neuropathy may be induced in both juvenile and adult rats treated with DCA at doses similar to those in clinical use. Dichloroacetate-induced peripheral neuropathy primarily afflicts axons and involves both metabolic and structural disorders. The DCA-treated rat may provide insight into the pathogenesis of this peripheral neuropathy and facilitate development of adjuvant therapeutics to prevent this disorder that currently restricts the clinical use of DCA.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doenças do Sistema Nervoso Periférico
/
Ácido Dicloroacético
/
Hipestesia
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
J Neuropathol Exp Neurol
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos