Peripheral neuropathy in rats exposed to dichloroacetate.

Full 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.

Author information

Author/s: Calcutt, Nigel A (NA); Lopez, Veronica L (VL); Bautista, Arjel D (AD); Mizisin, Leah M (LM); Torres, Brenda R (BR); Shroads, Albert L (AL); Mizisin, Andrew P (AP); Stacpoole, Peter W (PW);

Affiliation: Department of Pathology, University of California San Diego, La Jolla, California, USA. ncalcutt(-atsign-)ucsd.edu

Grants: ES007355 (Agency:NIEHS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: Journal of neuropathology and experimental neurology (J Neuropathol Exp Neurol), published in United States. (Language: eng)

Reference: 2009-Sep; vol 68 (issue 9) : pp 985-93

Dates: Created 2009/09/04; Completed 2009/10/01;

PMID: 19680144, status: MEDLINE (last retrieval date: 10/1/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.