Linked Life Data

16291825

Source:http://linkedlifedata.com/resource/pubmed/id/16291825

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-1-12
pubmed:abstractText
The neurotoxic hazard of a dithiocarbamate is influenced by route of exposure and acid stability of the dithiocarbamate. As an example, oral administration of the acid labile dithiocarbamate N,N-diethyldithiocarbamate (DEDC) causes a central-peripheral axonopathy thought to result from acid-promoted decomposition to CS2 in the stomach. In contrast, parenteral administration of DEDC, which bypasses the acidic environment of the stomach, causes a primary demyelination that is thought to be mediated through the intact parent dithiocarbamate. The relative acid stability of pyrrolidine dithiocarbamate (PDTC) suggests that a significant portion of a dose can be absorbed intact following oral exposure with the potential to produce a primary myelin injury. The present study was performed to characterize the neurotoxicity of PDTC and evaluate the possible role of copper in dithiocarbamate-mediated demyelination. Male Sprague Dawley rats were administered PDTC in drinking water and given either a normal- or high-copper diet for 18, 47, or 58 weeks. Examination of peripheral nerve by light microscopy and electron microscopy at the end of exposures revealed primary myelin lesions and axonal degeneration in the PDTC groups, with a significant increase in the severity of several lesions observed for the PDTC, high-copper group relative to the PDTC normal-copper diet. ICP-AES metal analysis determined that the PDTC groups had significantly increased brain copper, and at 58 weeks a significant increase in copper was seen in the sciatic nerve of PDTC high-copper animals relative to PDTC normal-copper diet animals. Although RP-HPLC analysis could not detect globin alkylaminocarbonyl cysteine modifications analogous to those seen with parenteral DEDC, LC/MS/MS identified (pyrrolidin-1-yl carbonyl)cysteine adducts on PDTC-exposed rat globin. These findings are consistent with previous studies supporting the ability of acid-stable dithiocarbamates to mediate myelin injury following oral exposure. The greater severity of lesions associated with dietary copper supplementation and elevated copper levels in nerve also suggests that perturbation of copper homeostasis may contribute to the development of myelin lesions.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1096-6080
pubmed:author
pubmed:issnType
Print
pubmed:volume
89
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
485-94
pubmed:dateRevised
2010-9-17
pubmed:meshHeading
pubmed-meshheading:16291825-Administration, Oral, pubmed-meshheading:16291825-Animals, pubmed-meshheading:16291825-Chromatography, Liquid, pubmed-meshheading:16291825-Copper, pubmed-meshheading:16291825-Demyelinating Diseases, pubmed-meshheading:16291825-Diet, pubmed-meshheading:16291825-Dose-Response Relationship, Drug, pubmed-meshheading:16291825-Drug Synergism, pubmed-meshheading:16291825-Environmental Pollutants, pubmed-meshheading:16291825-Globins, pubmed-meshheading:16291825-Male, pubmed-meshheading:16291825-Mass Spectrometry, pubmed-meshheading:16291825-Microscopy, Electron, pubmed-meshheading:16291825-Peripheral Nerves, pubmed-meshheading:16291825-Pyrrolidines, pubmed-meshheading:16291825-Rats, pubmed-meshheading:16291825-Rats, Sprague-Dawley, pubmed-meshheading:16291825-Sciatic Nerve, pubmed-meshheading:16291825-Thiocarbamates, pubmed-meshheading:16291825-Tissue Distribution
pubmed:year
2006
pubmed:articleTitle
Dietary copper enhances the peripheral myelinopathy produced by oral pyrrolidine dithiocarbamate.
pubmed:affiliation
Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2561, USA. holly.valentine@vanderbilt.edu
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural