Blood concentration of carbon disulphide in "normal" subjects and in alcoholic subjects treated with disulfiram.

Brugnone, F; Maranelli, G; Zotti, S; Zanella, I; Paris, Paola De; Caroldi, Stefano; Betta, Alberto

doi:10.1136/oem.49.9.658

Cited by 10 publications

(11 citation statements)

References 9 publications

(1 reference statement)

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“…There is considerable support 787 DISULFIRAM NEUROTOXICITY J Neuropathol Exp Neurol, Vol 59, September, 2000 in the literature for the hypothesis that disulfiram mediates its neurotoxicity through release of a carbon disulfide (CS 2 ) metabolite (14,16,18,22). This hypothesis has been advanced based on the clinical similarity between disulfiram and CS 2 neuropathy and the measurement of CS 2 and CS 2 metabolites in the breath and urine, respectively, following administration of disulfiram (23,24). CS 2 is a well-documented neurotoxicant that produces a central-peripheral distal axonopathy characterized by the formation of axonal swellings, degeneration, and atrophy (25,26).…”

Section: Disulfiram (Bis(diethylthiocarbamoyl)disulfide or Antabusementioning

confidence: 99%

Disulfiram Produces a Non-Carbon Disulfide-Dependent Schwannopathy in the Rat

Tonkin¹,

Erve²,

Valentine³

2000

J Neuropathol Exp Neurol

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Abstract. Disulfiram is a dithiocarbamate drug used for alcohol aversion therapy that produces a distal sensorimotor peripheral neuropathy in certain individuals. Because carbon disulfide, a disulfiram metabolite, produces a peripheral neuropathy clinically similar to disulfiram, it has been postulated that disulfiram neuropathy results from CS 2 release in vivo. The current study evaluated the morphological changes produced by disulfiram and the contribution of CS 2 -mediated protein cross-linking to disulfiram-induced neuropathy. Male Sprague-Dawley rats were administered 1% w/w disulfiram in their feed for 2, 4, 5, or 7 wk, and erythrocyte spectrin, hemoglobin, and neurofilament preparations were isolated and the extent of cross-linking assessed by SDS-PAGE, RP-HPLC, and Western blotting, respectively. Spinal cord and peripheral nerve sections were obtained from separate treated animals and assessed by light and electron microscopy. Significant protein cross-linking was only detected in neurofilament preparations obtained after 7 wk of exposure. Morphological changes were observed after 4 wk exposure and consisted of vacuoles within the Schwann cell cytoplasm and segmental demyelination. No neurofilamentous axonal swellings were detected and no significant changes were observed in the CNS. Because disulfiram neuropathy lacks both the morphological changes and intermolecular cross-linking characteristic of CS 2 , we conclude that disulfiram neuropathy is not mediated by the axonal toxicant CS 2 ; instead, disulfiram appears to be a primary Schwann cell toxicant. Recognition of a diethylcarbamoyl adduct on globin and axonal proteins presents a novel putative neurotoxic mechanism for disulfiram.

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Section: Disulfiram (Bis(diethylthiocarbamoyl)disulfide or Antabusementioning

confidence: 99%

Disulfiram Produces a Non-Carbon Disulfide-Dependent Schwannopathy in the Rat

Tonkin¹,

Erve²,

Valentine³

2000

J Neuropathol Exp Neurol

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“…Carbon disulphide is present in the blood in normal subjects both as free and acid labile bound components. Brugnone et al . (1992) reported a median level of free carbon disulphide of 261 ng/l and acid labile levels of 636 ng/l.…”

Section: Discussionmentioning

confidence: 99%

CLINICAL STUDY: Quantification of breath carbon disulphide and acetone following a single dose of disulfiram (Antabuse) using selected ion flow tube mass spectrometry (SIFT‐MS)

2006

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Selected ion flow tube mass spectrometry (SIFT-MS) has been used to measure simultaneously the concentrations of both carbon disulphide and acetone in exhaled breath following the ingestion of a single dose of disulfiram (Antabuse). Carbon disulphide is a product of the metabolism of disulfiram and is excreted mainly through the lungs. Acetone is a product of normal metabolism and appears in the breath of all individuals. These breath analyses were performed in single exhalations and the results were available in real time. The levels of breath acetone and carbon disulphide were compared with levels obtained from a control subject who had not ingested disulfiram. Breath carbon disulphide was seen to increase from 15 p.p.b. to 618 p.p.b. over a 28-hour period, in the single individual tested, following ingestion of disulfiram, while acetone levels increased from 300 p.p.b. (normal) to over 4000 p.p.b. (greatly elevated). No such increases were seen in the breath of the control subject over the same period. An obvious positive correlation between breath carbon disulphide and acetone concentrations following disulfiram ingestion is seen and discussed.

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“…An alternative approach is represented by the measurement of CS 2 in blood where the compound exists partly in a free form while the majority is bound to amino acids or biological macromolecules, but can be released using acid and heat [Brugnone et al, 1992]. The use of bound CS 2 in blood for monitoring uptake during the working day appears less satisfactory than urinary TTCA, while CS 2 measurement in breath may only reflect exposure in the period just before sampling.…”

Section: Blood and Breath Analysismentioning

confidence: 97%

“…It seems reasonable to conclude that urinary CS 2 found in the general population should be considered to have derived in part from catabolic reaction of urine and partially from inhaled CS 2 present in polluted air. We remember that CS 2 is a natural, ubiquitous polluting agent derived from various natural sources such as volcanic activity, combustion of organic substances, biological processes, and industrial activity [Brugnone et al, 1992]. The influence of diet and particulary of cabbage consumption cannot be excluded, but at present there are no data on this issue.…”

Section: Confounding Factorsmentioning

confidence: 98%

“…In the literature it has been reported that TTCA is a human FIGURE 1. Relation between exposure to carbon disulfide in breathing zone (CI, mg/m 3 ) and carbon disulfide concentration in urine (C in urine , g/l); the values given are metabolite of other chemicals, such as dithiocarbamates [Brugnone et al, 1992]. These compounds are partly metabolized to form thiophosgene or CS 2 , which after formation of a glutathione conjugate followed by an enzymatic degradation and ring-closure reaction, are excreted in urine as TTCA.…”

Section: Urinary Ttca Assaymentioning

confidence: 98%

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