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
N1 - Funding Information:
We thank Jed W. Fahey and Katherine K. Stephenson for preparing and analyzing the broccoli sprout samples for human administration. The staffs of the Clinical Pharmacology Drug Development Unit and of the General Clinical Research Center, Johns Hopkins School of Medicine and Hospital provided expert assistance in carrying out the clinical studies. These studies were supported by grants from the American Institute for Cancer Research, the Cancer Research Foundation of America, a Program-Project Grant (PO1 CA44530) from the National Cancer Institute, Department of Health and Human Services, NCRR Grant RR00052, Department of Health and Human Services and gifts from the Lewis B. and Dorothy Cullman Foundation. The Johns Hopkins University and P. Talalay and members of his family are equity holders in Brassica Protection Products LLC (Brassica), which is involved in the commercialization of broccoli sprouts. P. Talalay is a scientific consultant to Brassica. The University is managing this agreement in accordance with its conflict of interest policies. No funding for the reported work was provided by Brassica. The human study (our designation HS47) was carried out in compliance with the protocols approved by the Joint Committee on Clinical Investigation of the Johns Hopkins Medical Institutions. The volunteers gave written informed consent. We thank Dr. Fung-Lung Chung, American Health Foundation, Valhalla, NY for providing details of the protocol for measuring plasma dithiocarbamates by hexane extraction.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2002
Y1 - 2002
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
SN - 0009-8981
VL - 316
SP - 43
EP - 53
JO - Clinica Chimica Acta
JF - Clinica Chimica Acta
IS - 1-2
ER -