Quantitative determination of dithiocarbamates in human plasma, serum, erythrocytes and urine: Pharmacokinetics of broccoli sprout isothiocyanates in humans

Lingxiang Ye, Albena T. Dinkova-Kostova, Kristina L. Wade, Yuesheng Zhang, Theresa A. Shapiro, Paul Talalay

Research output: Contribution to journalArticle

263 Citations (Scopus)

Abstract

Background: Humans are exposed to substantial quantities of isothiocyanates and glucosinolates from vegetables. Since dietary isothiocyanates are widely regarded as potentially important chemoprotectors against cancer, reliable methods for measuring the plasma and tissue pharmacokinetics of isothiocyanates and their dithiocarbamate metabolites are essential for defining dosing regimens. Methods: Isothiocyanates (ITC) and dithiocarbamates (DTC) react quantitatively with 1,2-benzenedithiol to produce 1,3-benzodithiole-2-thione that can be quantified spectroscopically. Although this cyclocondensation reaction has been highly useful for analyzing plant material and urine samples, the determination of DTC/ITC (the total quantity of DTC and ITC components in a sample that react in the cyclocondensation reaction) in blood and tissues has been hampered by their low levels and the high concentrations of proteins that interfere with the cyclocondensation reaction. The protein content of blood and tissues was reduced by the precipitation with polyethylene glycol (PEG) or ultrafiltration, and the sensitivity of the method was increased substantially by the solid phase extraction of the cyclocondensation product. Results: Pharmacokinetic measurements were made in four human volunteers who received single doses of about 200 μmol of broccoli sprout isothiocyanates (largely sulforaphane, with lesser amounts of iberin and erucin). Isothiocyanates were absorbed rapidly, reached peak concentrations of 0.943-2.27 μmol/l in plasma, serum and erythrocytes at 1 h after feeding and declined with first-order kinetics (half-life of 1.77±0.13 h). The cumulative excretion at 8 h was 58.3±2.8% of the dose. Clearance was 369±53 ml/min, indicating active renal tubular secretion. Conclusion: A sensitive and specific method for quantifying DTC levels in human plasma, serum, and erythrocytes has been devised. Determinations of ITC/DTC levels are important because: (i) dietary isothiocyanates are of potential value in reducing the risk of cancer, and (ii) humans are extensively exposed to DTC as fungicides, insecticides, pesticides and rubber vulcanization accelerators.

Original languageEnglish
Pages (from-to)43-53
Number of pages11
JournalClinica Chimica Acta
Volume316
Issue number1-2
DOIs
Publication statusPublished - 12 Jan 2002

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Isothiocyanates
Plasma (human)
Pharmacokinetics
Brassica
Erythrocytes
Urine
Serum
Tissue
Glucosinolates
Plasmas
Fungicides
Vulcanization
Solid Phase Extraction
Rubber
Vegetables
Ultrafiltration
Insecticides
Metabolites
Pesticides
Particle accelerators

Keywords

  • Broccoli sprouts
  • Dithiocarbamates
  • Glucosinolates
  • Isothiocyanates
  • Myrosinase
  • Pharmacokinetics
  • Sulforaphane

Cite this

@article{473657bf39a34a729680488ad5c912cd,
title = "Quantitative determination of dithiocarbamates in human plasma, serum, erythrocytes and urine: Pharmacokinetics of broccoli sprout isothiocyanates in humans",
abstract = "Background: Humans are exposed to substantial quantities of isothiocyanates and glucosinolates from vegetables. Since dietary isothiocyanates are widely regarded as potentially important chemoprotectors against cancer, reliable methods for measuring the plasma and tissue pharmacokinetics of isothiocyanates and their dithiocarbamate metabolites are essential for defining dosing regimens. Methods: Isothiocyanates (ITC) and dithiocarbamates (DTC) react quantitatively with 1,2-benzenedithiol to produce 1,3-benzodithiole-2-thione that can be quantified spectroscopically. Although this cyclocondensation reaction has been highly useful for analyzing plant material and urine samples, the determination of DTC/ITC (the total quantity of DTC and ITC components in a sample that react in the cyclocondensation reaction) in blood and tissues has been hampered by their low levels and the high concentrations of proteins that interfere with the cyclocondensation reaction. The protein content of blood and tissues was reduced by the precipitation with polyethylene glycol (PEG) or ultrafiltration, and the sensitivity of the method was increased substantially by the solid phase extraction of the cyclocondensation product. Results: Pharmacokinetic measurements were made in four human volunteers who received single doses of about 200 μmol of broccoli sprout isothiocyanates (largely sulforaphane, with lesser amounts of iberin and erucin). Isothiocyanates were absorbed rapidly, reached peak concentrations of 0.943-2.27 μmol/l in plasma, serum and erythrocytes at 1 h after feeding and declined with first-order kinetics (half-life of 1.77±0.13 h). The cumulative excretion at 8 h was 58.3±2.8{\%} of the dose. Clearance was 369±53 ml/min, indicating active renal tubular secretion. Conclusion: A sensitive and specific method for quantifying DTC levels in human plasma, serum, and erythrocytes has been devised. Determinations of ITC/DTC levels are important because: (i) dietary isothiocyanates are of potential value in reducing the risk of cancer, and (ii) humans are extensively exposed to DTC as fungicides, insecticides, pesticides and rubber vulcanization accelerators.",
keywords = "Broccoli sprouts, Dithiocarbamates, Glucosinolates, Isothiocyanates, Myrosinase, Pharmacokinetics, Sulforaphane",
author = "Lingxiang Ye and Dinkova-Kostova, {Albena T.} and Wade, {Kristina L.} and Yuesheng Zhang and Shapiro, {Theresa A.} and Paul Talalay",
year = "2002",
month = "1",
day = "12",
doi = "10.1016/S0009-8981(01)00727-6",
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pages = "43--53",
journal = "Clinica Chimica Acta",
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}

Quantitative determination of dithiocarbamates in human plasma, serum, erythrocytes and urine : Pharmacokinetics of broccoli sprout isothiocyanates in humans. / Ye, Lingxiang; Dinkova-Kostova, Albena T.; Wade, Kristina L.; Zhang, Yuesheng; Shapiro, Theresa A.; Talalay, Paul.

In: Clinica Chimica Acta, Vol. 316, No. 1-2, 12.01.2002, p. 43-53.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Quantitative determination of dithiocarbamates in human plasma, serum, erythrocytes and urine

T2 - Pharmacokinetics of broccoli sprout isothiocyanates in humans

AU - Ye, Lingxiang

AU - Dinkova-Kostova, Albena T.

AU - Wade, Kristina L.

AU - Zhang, Yuesheng

AU - Shapiro, Theresa A.

AU - Talalay, Paul

PY - 2002/1/12

Y1 - 2002/1/12

N2 - Background: Humans are exposed to substantial quantities of isothiocyanates and glucosinolates from vegetables. Since dietary isothiocyanates are widely regarded as potentially important chemoprotectors against cancer, reliable methods for measuring the plasma and tissue pharmacokinetics of isothiocyanates and their dithiocarbamate metabolites are essential for defining dosing regimens. Methods: Isothiocyanates (ITC) and dithiocarbamates (DTC) react quantitatively with 1,2-benzenedithiol to produce 1,3-benzodithiole-2-thione that can be quantified spectroscopically. Although this cyclocondensation reaction has been highly useful for analyzing plant material and urine samples, the determination of DTC/ITC (the total quantity of DTC and ITC components in a sample that react in the cyclocondensation reaction) in blood and tissues has been hampered by their low levels and the high concentrations of proteins that interfere with the cyclocondensation reaction. The protein content of blood and tissues was reduced by the precipitation with polyethylene glycol (PEG) or ultrafiltration, and the sensitivity of the method was increased substantially by the solid phase extraction of the cyclocondensation product. Results: Pharmacokinetic measurements were made in four human volunteers who received single doses of about 200 μmol of broccoli sprout isothiocyanates (largely sulforaphane, with lesser amounts of iberin and erucin). Isothiocyanates were absorbed rapidly, reached peak concentrations of 0.943-2.27 μmol/l in plasma, serum and erythrocytes at 1 h after feeding and declined with first-order kinetics (half-life of 1.77±0.13 h). The cumulative excretion at 8 h was 58.3±2.8% of the dose. Clearance was 369±53 ml/min, indicating active renal tubular secretion. Conclusion: A sensitive and specific method for quantifying DTC levels in human plasma, serum, and erythrocytes has been devised. Determinations of ITC/DTC levels are important because: (i) dietary isothiocyanates are of potential value in reducing the risk of cancer, and (ii) humans are extensively exposed to DTC as fungicides, insecticides, pesticides and rubber vulcanization accelerators.

AB - Background: Humans are exposed to substantial quantities of isothiocyanates and glucosinolates from vegetables. Since dietary isothiocyanates are widely regarded as potentially important chemoprotectors against cancer, reliable methods for measuring the plasma and tissue pharmacokinetics of isothiocyanates and their dithiocarbamate metabolites are essential for defining dosing regimens. Methods: Isothiocyanates (ITC) and dithiocarbamates (DTC) react quantitatively with 1,2-benzenedithiol to produce 1,3-benzodithiole-2-thione that can be quantified spectroscopically. Although this cyclocondensation reaction has been highly useful for analyzing plant material and urine samples, the determination of DTC/ITC (the total quantity of DTC and ITC components in a sample that react in the cyclocondensation reaction) in blood and tissues has been hampered by their low levels and the high concentrations of proteins that interfere with the cyclocondensation reaction. The protein content of blood and tissues was reduced by the precipitation with polyethylene glycol (PEG) or ultrafiltration, and the sensitivity of the method was increased substantially by the solid phase extraction of the cyclocondensation product. Results: Pharmacokinetic measurements were made in four human volunteers who received single doses of about 200 μmol of broccoli sprout isothiocyanates (largely sulforaphane, with lesser amounts of iberin and erucin). Isothiocyanates were absorbed rapidly, reached peak concentrations of 0.943-2.27 μmol/l in plasma, serum and erythrocytes at 1 h after feeding and declined with first-order kinetics (half-life of 1.77±0.13 h). The cumulative excretion at 8 h was 58.3±2.8% of the dose. Clearance was 369±53 ml/min, indicating active renal tubular secretion. Conclusion: A sensitive and specific method for quantifying DTC levels in human plasma, serum, and erythrocytes has been devised. Determinations of ITC/DTC levels are important because: (i) dietary isothiocyanates are of potential value in reducing the risk of cancer, and (ii) humans are extensively exposed to DTC as fungicides, insecticides, pesticides and rubber vulcanization accelerators.

KW - Broccoli sprouts

KW - Dithiocarbamates

KW - Glucosinolates

KW - Isothiocyanates

KW - Myrosinase

KW - Pharmacokinetics

KW - Sulforaphane

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U2 - 10.1016/S0009-8981(01)00727-6

DO - 10.1016/S0009-8981(01)00727-6

M3 - Article

C2 - 11750273

AN - SCOPUS:0036135910

VL - 316

SP - 43

EP - 53

JO - Clinica Chimica Acta

JF - Clinica Chimica Acta

SN - 0009-8981

IS - 1-2

ER -