Brain uptake of S-(1,2-dichlorovinyl)glutathione and S-(1,2-dichlorovinyl)-L-cysteine, the glutathione and cysteine S-conjugates of the neurotoxin dichloroacetylene.

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.