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 micromol 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 micromol/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.
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 micromol 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 micromol/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.
Authors: Stephanie M Tortorella; Simon G Royce; Paul V Licciardi; Tom C Karagiannis Journal: Antioxid Redox Signal Date: 2014-12-19 Impact factor: 8.401
Authors: Thomas W Kensler; Derek Ng; Steven G Carmella; Menglan Chen; Lisa P Jacobson; Alvaro Muñoz; Patricia A Egner; Jian Guo Chen; Geng Sun Qian; Tao Yang Chen; Jed W Fahey; Paul Talalay; John D Groopman; Jian-Min Yuan; Stephen S Hecht Journal: Carcinogenesis Date: 2011-11-01 Impact factor: 4.944
Authors: Jed W Fahey; Scott L Wehage; W David Holtzclaw; Thomas W Kensler; Patricia A Egner; Theresa A Shapiro; Paul Talalay Journal: Cancer Prev Res (Phila) Date: 2012-02-07
Authors: Besma Abbaoui; Christopher R Lucas; Ken M Riedl; Steven K Clinton; Amir Mortazavi Journal: Mol Nutr Food Res Date: 2018-08-29 Impact factor: 5.914
Authors: Olga Azarenko; Tatiana Okouneva; Keith W Singletary; Mary Ann Jordan; Leslie Wilson Journal: Carcinogenesis Date: 2008-10-23 Impact factor: 4.944
Authors: Kristin K Brown; Frances H Blaikie; Robin A J Smith; Joel D A Tyndall; Hongqi Lue; Jürgen Bernhagen; Christine C Winterbourn; Mark B Hampton Journal: J Biol Chem Date: 2009-09-23 Impact factor: 5.157