ABSTRACT
SCOPE: Several lines of evidence suggest that the consumption of cruciferous vegetables is beneficial to human health. Yet, underlying mechanisms and key molecular targets that are involved with achieving these benefits in humans are still not fully understood. To accelerate this research, we conduct a human study to identify potential molecular targets of crucifers for further study. This study aims to characterize plasma metabolite profiles in humans before and after consuming fresh broccoli sprouts (a rich dietary source of bioactive sulforaphane). METHODS AND RESULTS: Ten healthy adults consume fresh broccoli sprouts (containing 200 µmol sulforaphane equivalents) at time 0 and provide blood samples at 0, 3, 6, 12, 24, and 48 h. An untargeted metabolomics screen reveals that levels of several plasma metabolites are significantly different before and after sprout intake, including fatty acids (14:0, 14:1, 16:0, 16:1, 18:0, and 18:1), glutathione, glutamine, cysteine, dehydroepiandrosterone, and deoxyuridine monophosphate. Evaluation of all time points is conducted using paired t-test (R software) and repeated measures analysis of variance for a within-subject design (Progenesis QI). CONCLUSION: This investigation identifies several potential molecular targets of crucifers that may aid in studying established and emerging health benefits of consuming cruciferous vegetables and related bioactive compounds.
Subject(s)
Blood/metabolism , Brassica , Adult , Brassica/chemistry , Dehydroepiandrosterone/blood , Deoxyuracil Nucleotides/blood , Fatty Acids/blood , Female , Glutathione/blood , Humans , Isothiocyanates/analysis , Isothiocyanates/blood , Isothiocyanates/urine , Male , Metabolomics/methods , Middle Aged , SulfoxidesABSTRACT
PURPOSE: The aim of the study is to determine the reliability during a 2-year period of several newly developed iron-related assays to assess their potential for use in prospective epidemiologic studies. METHODS: We assessed the temporal reliability of several iron-related assays by using three serum samples collected at yearly intervals from 50 postmenopausal participants in a large prospective study. RESULTS: We observed high reliability coefficients for ferritin (0.78; 95% confidence interval [CI], 0.67-0.86), soluble transferrin receptor (sTfR; 0.79; 95% CI, 0.69-0.87), sTfR/ferritin ratio (0.74; 95% CI, 0.62-0.83), and hepcidin (0.89; 95% CI, 0.84-0.94). In a subset of 30 women, lower reliability was observed for serum iron (0.50; 95% CI, 0.29-0.70), unsaturated iron-binding capacity (0.55; 95% CI, 0.34-0.73), total iron-binding capacity (0.60; 95% CI, 0.40-0.76), and serum transferrin saturation rate (0.44; 95% CI, 0.22-0.65). The reliability of anti-5-hydroxymethyl-2'-deoxyuridine autoantibody titers, a biomarker of oxidized DNA damage, one of the mechanisms by which iron is thought to impact disease risk, was very high (0.97, 95% CI, 0.5-0.99). CONCLUSIONS: Our results show that some newly developed iron-related assays could be useful tools to assess iron-disease associations in prospective cohorts that collect a single blood sample.
Subject(s)
Biomarkers/blood , Blood Chemical Analysis/standards , Ferritins/blood , Iron/blood , Postmenopause/blood , Adult , Analysis of Variance , Autoantibodies/blood , Blood Chemical Analysis/methods , Deoxyuracil Nucleotides/blood , Enzyme-Linked Immunosorbent Assay , Female , Ferritins/analysis , Humans , Middle Aged , New York City , Prospective Studies , Reproducibility of Results , Surveys and Questionnaires , Transferrin/analysisABSTRACT
Similar to HIV-1-induced suppression of thymus-derived lymphocytes (T cells), oxidatively stressed T cells show inhibited DNA synthesis and proliferation. The influence of oxidative stress on nucleotide pools was explored using 3H-uridine addition to OKT3-stimulated peripheral blood lymphocytes. The cells were preincubated and stimulated in the presence of 1 mM buthionine sulfoximine to inhibit GSH synthesis. This treatment gave rise to a significant reduction in dUDP and TTP biosynthesis following 18-32 hours stimulation, indicating possible impairment of ribonucleotide reductase activity.
Subject(s)
Lymphocytes/metabolism , Nucleotides/blood , Oxidative Stress/physiology , Buthionine Sulfoximine , Cell Cycle , Cells, Cultured , Chromatography, High Pressure Liquid , Deoxyuracil Nucleotides/blood , Enzyme Inhibitors/pharmacology , Glutathione/blood , Humans , Lymphocyte Activation , Lymphocytes/immunology , Methionine Sulfoximine/analogs & derivatives , Methionine Sulfoximine/pharmacology , Muromonab-CD3/immunology , Thymine Nucleotides/blood , Uridine/bloodABSTRACT
New water soluble derivatives of oxysterols--the phosphodiesters of oxysterols and of nucleosides--have been synthesized. In vitro, these compounds share the biological properties of their parent oxysterols. Furthermore, they display anticancer activity when injected i.p. in mice bearing experimental tumors. The pharmacokinetic study described here proved that the water-soluble derivatives of oxysterols act as prodrugs releasing free oxysterol in the blood, the liver and the kidney after i.p. or i.v. injection in rats. The hydro-solubility of such compounds as well as their slow metabolism into the active principle could account for their biological activity and make them suitable as new therapeutic agents.
