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Usage

Uses

Used in Pharmaceutical and Toxicological Research:
S-(1,2-dichlorovinyl)cysteine is used as a model compound for inducing acute renal failure and cataracts in experimental animals. This allows researchers to study the biochemical, physiological, and molecular mechanisms underlying these diseases and develop potential treatments.
Used in Environmental and Occupational Health Studies:
As a mutagenic and nephrotoxic metabolite, S-(1,2-dichlorovinyl)cysteine is used in studies to assess the health risks associated with exposure to trichloroethylene in various settings, such as industrial workplaces and contaminated environments.
Used in Drug Development:
S-(1,2-dichlorovinyl)cysteine can be used in the development of drugs or therapies aimed at counteracting the harmful effects of trichloroethylene exposure, by targeting the specific mechanisms through which DCVC causes damage to the kidneys and other organs.

Environmental Fate

Human exposure to DCVC occurs only via potential formation of DCVC in vivo following trichloroethylene (TCE) exposure; therefore, no data are available in this regard.

Toxicity evaluation

Cell death is initiated by the metabolism of DCVC via renal cysteine conjugate b-lyase to a sulfur-containing reactive thiol radical that covalently binds to macromolecules. The findings that the nephrotoxicity and cataractogenesis of DCVC can be blocked by aminooxyacetic acid (a selective inhibitor of b-lyase) and probenecid (organic anion transport Encyclopedia of inhibitor) provide evidence for the roles of cysteine conjugate b-lyase and the organic anion transport system, respectively, in DCVC-induced nephrotoxicity. Although the b-lyase enzyme is considered to be the major bioactivating enzyme for DCVC, other bioactivating enzyme activities have been described, and some of these may have relevance to risk assessment. Studies have shown that renal FMO3 can also metabolize DCVC to form DCVC sulfoxide thereby causing nephrotoxicity. Reports from several laboratories indicate that the cytotoxicity of DCVC is mediated at the mitochondrial level. Depletion of GSH, mitochondrial lipid peroxidation and GSSG formation, inhibition of mitochondrial lipoyl dehydrogenase activity, release of Ca2+ from mitochondria, and inhibition of mitochondrial membrane potential have been observed prior to renal cell death and correlated well with cytotoxicity.

InChI:InChI=1/C5H7Cl2NO2S/c6-1-4(7)11-2-3(8)5(9)10/h1,3H,2,8H2,(H,9,10)/b4-1+/t3-/m0/s1

Upstream product

• 2148-31-4 N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine 
• 52-90-4 L-Cysteine 
• 79-01-6 Trichloroethylene 

Downstream Products

• 189082-79-9 S-Vinyl-cystein-S-oxid 

Relevant academic research and scientific papers

Renal and hepatic toxicity of trichloroethylene and its glutathione-derived metabolites in rats and mice: Sex-, species-, and tissue-dependent differences

Acute cytotoxicity (lactate dehydrogenase release) of trichloroethylene (TRI), S-(1,2-dichlorovinyl)glutathione (DCVG), and S-(1,2-dichlorovinyl)-L-cysteine (DCVC) in freshly isolated renal cortical cells and hepatocytes from male and female rats was evaluated to test the hypothesis that the assay provides a valid indicator of sex- and tissue-dependent differences in sensitivity to TRI and its metabolites. We then determined mitochondrial toxicity (inhibition of state-3 and/or stimulation of state-4 respiration) in renal cortical and hepatic mitochondria from male and female rats and mice to assess sex-, tissue-, and species-dependent susceptibility. TRI was moderately cytotoxic in renal cells from male rats but was nontoxic in renal cells from female rats or hepatocytes from male or female rats. Acute cytotoxicity of both DCVG and DCVC was greater in renal cells from male rats than in renal cells from female rats. Although DCVC does not target the liver in vivo, it was a very potent hepatotoxicant in vitro. Mitochondrial toxicity in kidney and liver showed similar patterns, with mitochondria from male rats being more sensitive than mitochondria from female rats; order of potency was DCVC > DCVG ? TRI. State-3 respiration in mitochondria from mice was also inhibited, but the patterns and relative sensitivities differed from those in mitochondria from rats. Renal and hepatic mitochondria from mice were less sensitive than corresponding mitochondria from rats and renal mitochondria from female mice were significantly more sensitive than renal mitochondria from male mice. Thus, many of the species-, sex-, and tissue-dependent differences in toxicity observed in vivo are also observed in vitro.

Acylase-catalyzed deacetylation of haloalkene-derived mercapturates

Mercapturates (S-substituted N-acetyl-L-cysteines) are terminal metabolites formed by the glutathione-dependent metabolism of electrophilic xenobiotics, including haloalkenes. Acylases catalyze the hydrolysis of N- acyl-L-amino acids, including many xenobiotic-derived mercapturates, to give fatty acids and amino acids as products. Although several acylases have been identified, the acylases that catalyze the deacetylation of the haloalkene- derived mercapturates have not been identified and characterized. Acylase I catalyzes the deacetylation of some haloalkene-derived mercapturates, including S-(1,1,2,2-tetrafluoroethyl)-N-acetyl-L-cysteine, S-(2-chloro- 1,1,2-trifluoroethyl)-N-acetyl-L-cysteine, and S-(2-bromo-1,1,2- trifluoroethyl)-N-acetyl-L-cysteine [Uttamsingh, V., et al. (1998) Chem. Res. Toxicol. 11, 800-809]. In the studies presented here, we identified a rat kidney acylase that catalyzed the hydrolysis of the haloalkene-derived mercapturates S-(1,2-dichlorovinyl)-N-acetyl-L-cysteine, S-(1,2,3,4,4- pentachloro-1,3-butadienyl)-N-acetyl-L-cysteine, and S-(2,2-dibromo-1,1- difluoroethyl)-N-acetyl-L-cysteine. The substrate selectivity and amino acid sequence of the purified rat kidney acylase were studied. Although the sequence of the purified rat kidney acylase was somewhat identical with that of aspartoacylase, it did not catalyze the hydrolysis of N-acetyl-L- aspartate.