Abstract |
Dichloroacetylene causes trigeminal neuropathy in humans and animals. Glutathione conjugation of dichloroacetylene affords S-(1,2-dichlorovinyl)glutathione (DCVG), which is hydrolyzed to S-(1,2-dichlorovinyl)-L-cysteine (DCVC). This study was undertaken to test the hypothesis that the neurotoxicity of dichloroacetylene may be associated with glutathione S-conjugate formation and brain uptake and bioactivation of the dichloroacetylene-derived S-conjugates. With the Oldendorf technique, the Brain Uptake Index for [35S]DCVC and [35S]DCVG was determined and compared with the uptake of [35S] methionine and [14C] sucrose. Brain uptake of DCVC exceeded uptake of methionine and DCVG uptake was comparable to methionine uptake. Both [35S]DCVC and [35S]DCVG were recovered intact in brain tissue. The uptake of the 35S-labeled S-conjugates was inhibited by unlabeled DCVC and DCVG in a concentration-dependent manner. The data indicated that DCVC, but not DCVG, was transported by the sodium-independent system-L transporter for neutral amino acids. In vitro studies revealed that DCVG can be hydrolyzed to DCVC by brain tissue in a concentration-dependent manner.
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Authors | N J Patel, J S Fullone, M W Anders |
Journal | Brain research. Molecular brain research
(Brain Res Mol Brain Res)
Vol. 17
Issue 1-2
Pg. 53-8
(Jan 1993)
ISSN: 0169-328X [Print] Netherlands |
PMID | 8381909
(Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Neurotoxins
- S-(1,2-dichlorovinyl)cysteine
- dichloroacetylene
- S-(1,2-dichlorovinyl)glutathione
- Glutathione
- Cysteine
- Acetylene
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Topics |
- Acetylene
(analogs & derivatives, pharmacokinetics)
- Animals
- Biological Transport
- Biotransformation
- Blood-Brain Barrier
- Brain
(metabolism)
- Cysteine
(analogs & derivatives, pharmacokinetics)
- Glutathione
(analogs & derivatives, pharmacokinetics)
- Neurotoxins
(pharmacokinetics)
- Rats
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