The Experts below are selected from a list of 252 Experts worldwide ranked by ideXlab platform
Thomas Göen - One of the best experts on this subject based on the ideXlab platform.
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s alkyl Mercapturic Acids methyl Mercapturic Acid ethyl Mercapturic Acid n propyl Mercapturic Acid und iso propyl Mercapturic Acid in urine biomonitoring methods 2015
The MAK Collection for Occupational Health and Safety, 2016Co-Authors: Elisabeth Eckert, Thomas Göen, A HartwigAbstract:The analytical method permits simultaneous determination of various alkyl Mercapturic Acids in urine. For determination, the urine samples are buffered to pH = 2.5, spiked with isotope labeled internal standards (d3-MeMA, d5-EtMA, d7-PrMA and d7-iPrMA), processed using online solid phase extraction (online SPE) and analyzed. For that purpose the analytes are enriched on a C18 preconcentration column [Restricted Access Material (RAM) phase] and separated from most of the matrix. Subsequently, the analytes are transferred in backflush mode from the RAM phase to the analytical column, separated chromatographically and finally subjected to tandem mass spectrometric detection. For quantification, a calibration is carried out using standard solutions in pooled urine which are processed and analyzed in the same way as the samples to be analyzed. Keywords: Biomonitoring; 1-bromopropane; 2-bromopropane; ethyl bromide; bromoethane; methyl bromide; bromomethane; dimethyl sulfate; diethyl sulfate; S-alkyl Mercapturic Acids; methyl Mercapturic Acid; ethyl Mercapturic Acid; n-propyl Mercapturic Acid; iso-propyl Mercapturic Acid; urine; high-performance liquid chromatography; tandem mass spectrometric detection; LC–MS/MS; analysis in biological materials; occupational monitoring; analytical method; biomarker; metabolites; alkylating compounds; alkylating agents
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The MAK Collection for Occupational Health and Safety - S-Alkyl Mercapturic Acids (methyl Mercapturic Acid, ethyl Mercapturic Acid, n-propyl Mercapturic Acid und iso-propyl Mercapturic Acid) in urine [Biomonitoring Methods, 2015]
The MAK-Collection for Occupational Health and Safety, 2016Co-Authors: Elisabeth Eckert, Thomas Göen, A HartwigAbstract:The analytical method permits simultaneous determination of various alkyl Mercapturic Acids in urine. For determination, the urine samples are buffered to pH = 2.5, spiked with isotope labeled internal standards (d3-MeMA, d5-EtMA, d7-PrMA and d7-iPrMA), processed using online solid phase extraction (online SPE) and analyzed. For that purpose the analytes are enriched on a C18 preconcentration column [Restricted Access Material (RAM) phase] and separated from most of the matrix. Subsequently, the analytes are transferred in backflush mode from the RAM phase to the analytical column, separated chromatographically and finally subjected to tandem mass spectrometric detection. For quantification, a calibration is carried out using standard solutions in pooled urine which are processed and analyzed in the same way as the samples to be analyzed. Keywords: Biomonitoring; 1-bromopropane; 2-bromopropane; ethyl bromide; bromoethane; methyl bromide; bromomethane; dimethyl sulfate; diethyl sulfate; S-alkyl Mercapturic Acids; methyl Mercapturic Acid; ethyl Mercapturic Acid; n-propyl Mercapturic Acid; iso-propyl Mercapturic Acid; urine; high-performance liquid chromatography; tandem mass spectrometric detection; LC–MS/MS; analysis in biological materials; occupational monitoring; analytical method; biomarker; metabolites; alkylating compounds; alkylating agents
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The MAK Collection for Occupational Health and Safety - Mercapturic Acids of 2‐chloroprene, epichlorohydrin, and 1,3‐butadiene in urine [Biomonitoring Methods, 2015]
The MAK-Collection for Occupational Health and Safety, 2016Co-Authors: Elisabeth Eckert, Thomas Göen, A HartwigAbstract:The analytical method permits simultaneous determination of the Mercapturic Acid of epichlorohydrin i.e. N-acetyl-S-(3-chloro-2-hydroxypropyl) cysteine (CHPMA) and of four Mercapturic Acids of 2-chloroprene in urine: N-acetyl-S-(4-chloro-3-oxobutyl) cysteine (Cl-MA I), N-acetyl-S-(3-chloro-2-hydroxy-3-butenyl) cysteine (Cl-MA III), N-acetyl-S-(4-hydroxy-3-oxobutyl) cysteine (HOBMA) and N-acetyl-S-(3,4-dihydroxybutyl) cysteine (DHBMA). The Mercapturic Acids HOBMA and DHBMA are also formed after exposure to 1,3-butadiene. For determination, the urine samples are buffered to pH 2.5, spiked with isotopelabeled internal standards (d3-CHPMA, d3-Cl-MA I, d3-Cl-MA III, d3-HOBMA and d7-DHBMA), processed using online solid phase extraction (online SPE) and LC–MS/MS. For that purpose the analytes are enriched on a C18 pre-concentration column [RAM (Restricted Access Material) phase]. Subsequently, the analytes are transferred in backflush mode from the RAM phase to the analytical column, separated chromatographically and finally subjected to tandem mass spectrometric detection. Calibration is carried out using standard solutions in pooled urine which are processed and analyzed in the same way as the samples to be analyzed. Keywords: Biomonitoring; 2-chloroprene; epichlorohydrin; 1,3-butadiene; 4-chloro-3-oxobutyl Mercapturic Acid; 3-chloro-2-hydroxy-3-butenyl Mercapturic Acid; 4-hydroxy-3-oxobutyl Mercapturic Acid; HOBMA; 3,4-dihydroxybutyl Mercapturic Acid; DHBMA; 3-chloro-2-hydroxypropyl Mercapturic Acid; CHPMA; urine; high-performance liquid chromatography; tandem mass spectrometric detection; LC–MS/MS; analysis in biological materials; occupational monitoring; analytical method; biomarker; metabolites
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Excretion of Mercapturic Acids in human urine after occupational exposure to 2-chloroprene.
Archives of toxicology, 2013Co-Authors: Elisabeth Eckert, Gabriele Leng, Wolfgang Gries, Thomas GöenAbstract:A pilot study was conducted for human biomonitoring of the suspected carcinogen 2-chloroprene. For this purpose, urine samples of 14 individuals occupationally exposed to 2-chloroprene (exposed group) and of 30 individuals without occupational exposure to alkylating substances (control group) were analysed for six potential Mercapturic Acids of 2-chloroprene: 4-chloro-3-oxobutyl Mercapturic Acid (Cl-MA-I), 4-chloro-3-hydroxybutyl Mercapturic Acid (Cl-MA-II), 3-chloro-2-hydroxy-3-butenyl Mercapturic Acid (Cl-MA-III), 4-hydroxy-3-oxobutyl Mercapturic Acid (HOBMA), 3,4-dihydroxybutyl Mercapturic Acid (DHBMA) and 2-hydroxy-3-butenyl Mercapturic Acid (MHBMA). In direct comparison with the control group, elevated levels of the Mercapturic Acids Cl-MA-III, MHBMA, HOBMA and DHBMA were found in the urine samples of the exposed group. Cl-MA-I and Cl-MA-II were not detected in any of the samples, whereas HOBMA and DHBMA were found in all analysed urine samples. Thus, for the first time, it was possible to detect HOBMA and Cl-MA-III in human urine. The Mercapturic Acid Cl-MA-III could be confirmed as a specific metabolite of 2-chloroprene in humans providing evidence for the intermediate formation of a reactive epoxide during biotransformation. The main metabolite, however, was found to be DHBMA showing a distinct and significant correlation with the urinary Cl-MA-III levels in the exposed group. The obtained results give new scientific insight into the course of biotransformation of 2-chloroprene in humans.
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A method for the simultaneous determination of Mercapturic Acids as biomarkers of exposure to 2-chloroprene and epichlorohydrin in human urine.
Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2012Co-Authors: Elisabeth Eckert, Gabriele Leng, Wolfgang Gries, Thomas GöenAbstract:We developed and validated an analytical method for the simultaneous determination of several chlorine and non-chlorine containing Mercapturic Acids in urine as specific metabolites of the hazardous chemicals 2-chloroprene and epichlorohydrin. The method involves an online column switching arrangement for online solid phase extraction of the analytes with subsequent analytical separation and detection using LC-MS/MS. The developed method enables for the first time the determination of Cl-MA-I (4-chloro-3-oxobutyl Mercapturic Acid), Cl-MA-II (4-chloro-3-hydroxybutyl Mercapturic Acid), Cl-MA-III (3-chloro-2-hydroxy-3-butenyl Mercapturic Acid) and HOBMA (4-hydroxy-3-oxobutyl Mercapturic Acid) as potential biomarkers of 2-chloroprene in urine. Additionally, CHPMA (3-chloro-2-hydroxypropyl Mercapturic Acid) as a specific metabolite of epichlorohydrin in urine and DHBMA (3,4-dihydroxybutyl Mercapturic Acid) can be determined. The analytical method proved to be both sensitive and reliable with detection limits ranging from 1.4 μg/L (for Cl-MA-III) to 4.2 μg/L (for HOBMA). Intra- and interday imprecision was determined to range from 4.7 to 11.8%. Due to the good accuracy and precision and the low limits of detection the developed method is well suited for application in biomonitoring studies in order to determine occupational exposure to 2-chloroprene and epichlorohydrin.
Elisabeth Eckert - One of the best experts on this subject based on the ideXlab platform.
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s alkyl Mercapturic Acids methyl Mercapturic Acid ethyl Mercapturic Acid n propyl Mercapturic Acid und iso propyl Mercapturic Acid in urine biomonitoring methods 2015
The MAK Collection for Occupational Health and Safety, 2016Co-Authors: Elisabeth Eckert, Thomas Göen, A HartwigAbstract:The analytical method permits simultaneous determination of various alkyl Mercapturic Acids in urine. For determination, the urine samples are buffered to pH = 2.5, spiked with isotope labeled internal standards (d3-MeMA, d5-EtMA, d7-PrMA and d7-iPrMA), processed using online solid phase extraction (online SPE) and analyzed. For that purpose the analytes are enriched on a C18 preconcentration column [Restricted Access Material (RAM) phase] and separated from most of the matrix. Subsequently, the analytes are transferred in backflush mode from the RAM phase to the analytical column, separated chromatographically and finally subjected to tandem mass spectrometric detection. For quantification, a calibration is carried out using standard solutions in pooled urine which are processed and analyzed in the same way as the samples to be analyzed. Keywords: Biomonitoring; 1-bromopropane; 2-bromopropane; ethyl bromide; bromoethane; methyl bromide; bromomethane; dimethyl sulfate; diethyl sulfate; S-alkyl Mercapturic Acids; methyl Mercapturic Acid; ethyl Mercapturic Acid; n-propyl Mercapturic Acid; iso-propyl Mercapturic Acid; urine; high-performance liquid chromatography; tandem mass spectrometric detection; LC–MS/MS; analysis in biological materials; occupational monitoring; analytical method; biomarker; metabolites; alkylating compounds; alkylating agents
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The MAK Collection for Occupational Health and Safety - S-Alkyl Mercapturic Acids (methyl Mercapturic Acid, ethyl Mercapturic Acid, n-propyl Mercapturic Acid und iso-propyl Mercapturic Acid) in urine [Biomonitoring Methods, 2015]
The MAK-Collection for Occupational Health and Safety, 2016Co-Authors: Elisabeth Eckert, Thomas Göen, A HartwigAbstract:The analytical method permits simultaneous determination of various alkyl Mercapturic Acids in urine. For determination, the urine samples are buffered to pH = 2.5, spiked with isotope labeled internal standards (d3-MeMA, d5-EtMA, d7-PrMA and d7-iPrMA), processed using online solid phase extraction (online SPE) and analyzed. For that purpose the analytes are enriched on a C18 preconcentration column [Restricted Access Material (RAM) phase] and separated from most of the matrix. Subsequently, the analytes are transferred in backflush mode from the RAM phase to the analytical column, separated chromatographically and finally subjected to tandem mass spectrometric detection. For quantification, a calibration is carried out using standard solutions in pooled urine which are processed and analyzed in the same way as the samples to be analyzed. Keywords: Biomonitoring; 1-bromopropane; 2-bromopropane; ethyl bromide; bromoethane; methyl bromide; bromomethane; dimethyl sulfate; diethyl sulfate; S-alkyl Mercapturic Acids; methyl Mercapturic Acid; ethyl Mercapturic Acid; n-propyl Mercapturic Acid; iso-propyl Mercapturic Acid; urine; high-performance liquid chromatography; tandem mass spectrometric detection; LC–MS/MS; analysis in biological materials; occupational monitoring; analytical method; biomarker; metabolites; alkylating compounds; alkylating agents
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The MAK Collection for Occupational Health and Safety - Mercapturic Acids of 2‐chloroprene, epichlorohydrin, and 1,3‐butadiene in urine [Biomonitoring Methods, 2015]
The MAK-Collection for Occupational Health and Safety, 2016Co-Authors: Elisabeth Eckert, Thomas Göen, A HartwigAbstract:The analytical method permits simultaneous determination of the Mercapturic Acid of epichlorohydrin i.e. N-acetyl-S-(3-chloro-2-hydroxypropyl) cysteine (CHPMA) and of four Mercapturic Acids of 2-chloroprene in urine: N-acetyl-S-(4-chloro-3-oxobutyl) cysteine (Cl-MA I), N-acetyl-S-(3-chloro-2-hydroxy-3-butenyl) cysteine (Cl-MA III), N-acetyl-S-(4-hydroxy-3-oxobutyl) cysteine (HOBMA) and N-acetyl-S-(3,4-dihydroxybutyl) cysteine (DHBMA). The Mercapturic Acids HOBMA and DHBMA are also formed after exposure to 1,3-butadiene. For determination, the urine samples are buffered to pH 2.5, spiked with isotopelabeled internal standards (d3-CHPMA, d3-Cl-MA I, d3-Cl-MA III, d3-HOBMA and d7-DHBMA), processed using online solid phase extraction (online SPE) and LC–MS/MS. For that purpose the analytes are enriched on a C18 pre-concentration column [RAM (Restricted Access Material) phase]. Subsequently, the analytes are transferred in backflush mode from the RAM phase to the analytical column, separated chromatographically and finally subjected to tandem mass spectrometric detection. Calibration is carried out using standard solutions in pooled urine which are processed and analyzed in the same way as the samples to be analyzed. Keywords: Biomonitoring; 2-chloroprene; epichlorohydrin; 1,3-butadiene; 4-chloro-3-oxobutyl Mercapturic Acid; 3-chloro-2-hydroxy-3-butenyl Mercapturic Acid; 4-hydroxy-3-oxobutyl Mercapturic Acid; HOBMA; 3,4-dihydroxybutyl Mercapturic Acid; DHBMA; 3-chloro-2-hydroxypropyl Mercapturic Acid; CHPMA; urine; high-performance liquid chromatography; tandem mass spectrometric detection; LC–MS/MS; analysis in biological materials; occupational monitoring; analytical method; biomarker; metabolites
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Excretion of Mercapturic Acids in human urine after occupational exposure to 2-chloroprene.
Archives of toxicology, 2013Co-Authors: Elisabeth Eckert, Gabriele Leng, Wolfgang Gries, Thomas GöenAbstract:A pilot study was conducted for human biomonitoring of the suspected carcinogen 2-chloroprene. For this purpose, urine samples of 14 individuals occupationally exposed to 2-chloroprene (exposed group) and of 30 individuals without occupational exposure to alkylating substances (control group) were analysed for six potential Mercapturic Acids of 2-chloroprene: 4-chloro-3-oxobutyl Mercapturic Acid (Cl-MA-I), 4-chloro-3-hydroxybutyl Mercapturic Acid (Cl-MA-II), 3-chloro-2-hydroxy-3-butenyl Mercapturic Acid (Cl-MA-III), 4-hydroxy-3-oxobutyl Mercapturic Acid (HOBMA), 3,4-dihydroxybutyl Mercapturic Acid (DHBMA) and 2-hydroxy-3-butenyl Mercapturic Acid (MHBMA). In direct comparison with the control group, elevated levels of the Mercapturic Acids Cl-MA-III, MHBMA, HOBMA and DHBMA were found in the urine samples of the exposed group. Cl-MA-I and Cl-MA-II were not detected in any of the samples, whereas HOBMA and DHBMA were found in all analysed urine samples. Thus, for the first time, it was possible to detect HOBMA and Cl-MA-III in human urine. The Mercapturic Acid Cl-MA-III could be confirmed as a specific metabolite of 2-chloroprene in humans providing evidence for the intermediate formation of a reactive epoxide during biotransformation. The main metabolite, however, was found to be DHBMA showing a distinct and significant correlation with the urinary Cl-MA-III levels in the exposed group. The obtained results give new scientific insight into the course of biotransformation of 2-chloroprene in humans.
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A method for the simultaneous determination of Mercapturic Acids as biomarkers of exposure to 2-chloroprene and epichlorohydrin in human urine.
Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2012Co-Authors: Elisabeth Eckert, Gabriele Leng, Wolfgang Gries, Thomas GöenAbstract:We developed and validated an analytical method for the simultaneous determination of several chlorine and non-chlorine containing Mercapturic Acids in urine as specific metabolites of the hazardous chemicals 2-chloroprene and epichlorohydrin. The method involves an online column switching arrangement for online solid phase extraction of the analytes with subsequent analytical separation and detection using LC-MS/MS. The developed method enables for the first time the determination of Cl-MA-I (4-chloro-3-oxobutyl Mercapturic Acid), Cl-MA-II (4-chloro-3-hydroxybutyl Mercapturic Acid), Cl-MA-III (3-chloro-2-hydroxy-3-butenyl Mercapturic Acid) and HOBMA (4-hydroxy-3-oxobutyl Mercapturic Acid) as potential biomarkers of 2-chloroprene in urine. Additionally, CHPMA (3-chloro-2-hydroxypropyl Mercapturic Acid) as a specific metabolite of epichlorohydrin in urine and DHBMA (3,4-dihydroxybutyl Mercapturic Acid) can be determined. The analytical method proved to be both sensitive and reliable with detection limits ranging from 1.4 μg/L (for Cl-MA-III) to 4.2 μg/L (for HOBMA). Intra- and interday imprecision was determined to range from 4.7 to 11.8%. Due to the good accuracy and precision and the low limits of detection the developed method is well suited for application in biomonitoring studies in order to determine occupational exposure to 2-chloroprene and epichlorohydrin.
Yu Zhang - One of the best experts on this subject based on the ideXlab platform.
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metabolomics based biomarker analysis of dihydroxypropyl Mercapturic Acid isomers from 3 monochloropropane 1 2 diol and glycidol for evaluation of toxicokinetics in rats and daily internal exposure in humans
Talanta, 2019Co-Authors: Wei Jia, Xinyu Chen, Yiping Ren, Lei Mao, Hong Miao, Dawei Chen, Yu ZhangAbstract:Abstract 3-Monochloropropane-1,2-diol (3-MCPD), glycidol, and their esters are some major sources of risk factors during food processing. Here we showed the biomarker analysis of 2,3-dihydroxypropyl Mercapturic Acid (DHPMA) isomers which derived from the metabolism of 3-MCPD, glycidol, and their esters in urine of rats and humans. Iso-DHPMA, a novel urinary metabolite, was discovered and detected in urine of rats, which were orally administered with glycidol but not 3-MCPD. Using the quadrupole-orbitrap high-resolution mass spectrometry, we confirmed that iso-DHPMA appeared a specific biomarker which derived from glycidol. The limit of quantification (signal-to-noise ratio, 10:1) of the analytes in urine of rats and humans were 1.33 ng/mL and 1.56 ng/mL, respectively. Acceptable within-laboratory reproducibility (RSD
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toxicokinetics and internal exposure of acrylamide new insight into comprehensively profiling Mercapturic Acid metabolites as short term biomarkers in rats and chinese adolescents
Archives of Toxicology, 2017Co-Authors: Qiao Wang, Xinyu Chen, Yiping Ren, Qing Chen, Zhen Meng, Jun Cheng, Yunyan Zheng, Weijiang Zeng, Qingning Zhao, Yu ZhangAbstract:Acrylamide is classified as a probable carcinogen to humans and generated from Maillard reaction. Currently, the short-term exposure to acrylamide was evaluated via external diet sources in vitro or two main Mercapturic Acid metabolites: N-acetyl-S-(2-carbamoylethyl)-l-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-l-cysteine (GAMA) in vivo. In the present work, we comprehensively profiled four Mercapturic Acid metabolites and evaluated their internal exposure in rats and Chinese adolescents. The cumulative excretion of Mercapturic Acid metabolites contributes 38.4–73.0 and 43.8–63.6 % of total in vivo metabolites of acrylamide in male and female rats, respectively, when 1, 10, and 50 mg/kg bw of acrylamide were orally administered. Toxicokinetic study revealed that the conversion of acrylamide into glycidamide and glutathione coupling process is highly related to the gender and oral gavage dose via evaluating kinetic parameters, accumulative excretion percentages, and molar ratios of oxidative to reductive metabolism. In human study, a total of 101 Chinese adolescents (41 men and 60 women) were enrolled and served with a meal of potato chips, corresponding to a single-dose (12.6 μg/kg bw) exposure to acrylamide. Toxicokinetic work showed that AAMA is an early and predominant metabolite appearing as a biomarker in urine. N-acetyl-S-(2-carbamoylethyl)-l-cysteine-sulfoxide (AAMA-sul), an oxidative product from AAMA, exhibits a higher peak concentration than GAMA and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-l-cysteine (iso-GAMA) during the whole 48-h toxicokinetic period. The internal exposure via four Mercapturic Acid metabolites is associated with the gender and body mass index characteristics. Thus, current study aims at Mercapturic Acid metabolites as urinary biomarkers and provides comprehensive insights into the short-term internal exposure to acrylamide.
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comprehensive profiling of Mercapturic Acid metabolites from dietary acrylamide as short term exposure biomarkers for evaluation of toxicokinetics in rats and daily internal exposure in humans using isotope dilution ultra high performance liquid chro
Analytica Chimica Acta, 2015Co-Authors: Yu Zhang, Qiao Wang, Jun Cheng, Jingshun Zhang, Yiping RenAbstract:Mercapturic Acid metabolites from dietary acrylamide are important short-term exposure biomarkers for evaluating the in vivo toxicity of acrylamide. Most of studies have focused on the measurement of two metabolites, N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA). Thus, the comprehensive profile of acrylamide urinary metabolites cannot be fully understood. We developed an isotope dilution ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous determination of all four Mercapturic Acid adducts of acrylamide and its primary metabolite glycidamide under the electroscopy ionization negative (ESI-) mode in the present study. The limit of detection (LOD) and limit of quantification (LOQ) of the analytes ranged 0.1-0.3 ng/mL and 0.4-1.0 ng/mL, respectively. The recovery rates with low, intermediate and high spiking levels were calculated as 95.5%-105.4%, 98.2%-114.0% and 92.2%-108.9%, respectively. Acceptable within-laboratory reproducibility (RSD<7.0%) substantially supported the use of current method for robust analysis. Rapid pretreatment procedures and short run time (8 min per sample) ensured good efficiency of metabolism profiling, indicating a wide application for investigating short-term internal exposure of dietary acrylamide. Our proposed UHPLC-MS/MS method was successfully applied to the toxicokinetic study of acrylamide in rats. Meanwhile, results of human urine analysis indicated that the levels of N-acetyl-S-(2-carbamoylethyl)-L-cysteine-sulfoxide (AAMA-sul), which did not appear in the Mercapturic Acid metabolites in rodents, were more than the sum of GAMA and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (iso-GAMA). Thus, AAMA-sul may alternatively become a specific biomarker for investigating the acrylamide exposure in humans. Current proposed method provides a substantial methodology support for comprehensive profiling of toxicokinetics and daily internal exposure evaluations of acrylamide in vivo.
Françoise Guéraud - One of the best experts on this subject based on the ideXlab platform.
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A Helicobacter pylori-associated insulin resistance in asymptomatic sedentary young men does not correlate with inflammatory markers and urine levels of 8-iso-PGF2-α or 1,4-dihydroxynonane Mercapturic Acid
Archives of Physiology and Biochemistry, 2018Co-Authors: Andriy Cherkas, Françoise Guéraud, Sergii Golota, Orest Abrahamovych, Christoph Pichler, Armen Nersesyan, Volodymyr Krupak, Vira Bugiichyk, Ostap Yatskevych, Mykhaylo PliatskoAbstract:A potential contribution of H. pylori contamination to low-grade inflammation, oxidative stress (OS) and insulin resistance as well as correlations between these parameters in asymptomatic sedentary males was analysed. We enrolled 30 apparently healthy asymptomatic young subjects (18 H. pylori negative and 12 positive) and measured whole blood glucose, glycated haemoglobin, insulin, C-peptide, cortisol, aldosterone, testosterone, thyroid stimulating hormone, C-reactive protein, interleukins 6 and 10, TNF-alpha and comet assay. As markers of OS, we used urine levels of iso-PGF2-α and 1,4-dihydroxynonane Mercapturic Acid (DHN-MA). Twofold elevation of fasting insulin level and HOMA index in H. pylori-positive subjects (p
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new marker of colon cancer risk associated with heme intake 1 4 dihydroxynonane Mercapturic Acid
Cancer Epidemiology Biomarkers & Prevention, 2006Co-Authors: Fabrice Pierre, Géraldine Peiro, Sylviane Tache, Amanda J Cross, Nicole Gasc, Gaëlle Gottardi, Denis Corpet, Sheila Bingham, Françoise GuéraudAbstract:Background: Red meat consumption is associated with an increased risk of colon cancer. Animal studies show that heme, found in red meat, promotes preneoplastic lesions in the colon, probably due to the oxidative properties of this compound. End products of lipid peroxidation, such as 4-hydroxynonenal metabolites or 8- iso -prostaglandin-F2α (8- iso -PGF2α), could reflect this oxidative process and could be used as biomarkers of colon cancer risk associated with heme intake. Methods: We measured urinary excretion of 8- iso -PGF2α and 1,4-dihydroxynonane Mercapturic Acid (DHN-MA), the major urinary metabolite of 4-hydroxynonenal, in three studies. In a short-term and a carcinogenesis long-term animal study, we fed rats four different diets (control, chicken, beef, and blood sausage as a high heme diet). In a randomized crossover human study, four different diets were fed (a 60 g/d red meat baseline diet, 120 g/d red meat, baseline diet supplemented with heme iron, and baseline diet supplemented with non-heme iron). Results: DHN-MA excretion increased dramatically in rats fed high heme diets, and the excretion paralleled the number of preneoplastic lesions in azoxymethane initiated rats ( P < 0.0001). In the human study, the heme supplemented diet resulted in a 2-fold increase in DHN-MA ( P < 0.001). Urinary 8- iso -PGF2α increased moderately in rats fed a high heme diet ( P < 0.0001), but not in humans. Conclusion: Urinary DHN-MA is a useful noninvasive biomarker for determining the risk of preneoplastic lesions associated with heme iron consumption and should be further investigated as a potential biomarker of colon cancer risk. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2274–9)
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New marker of colon cancer risk associated with heme intake: 1,4-dihydroxynonane Mercapturic Acid
Cancer Epidemiology Biomarkers and Prevention, 2006Co-Authors: Fabrice Pierre, Géraldine Peiro, Sylviane Tache, Amanda J Cross, Sheila A Bingham, Nicole Gasc, Gaëlle Gottardi, Denis Corpet, Françoise GuéraudAbstract:Red meat consumption is associated with an increased risk of colon cancer. Animal studies showthat heme, found in redmeat, promotes preneoplastic lesions in the colon, probably due to the oxidative properties of this compound. End products of lipid peroxidation, such as 4-hydroxynonenal metabolites or 8-iso-prostaglandin-F2A (8-iso-PGF2A), could reflect this oxidative process and could be used as biomarkers of colon cancer risk associated with heme intake. Methods: We measured urinary excretion of 8-iso-PGF2A and 1,4-dihydroxynonane Mercapturic Acid (DHN-MA), the major urinary metabolite of 4-hydroxynonenal, in three studies. In a short-term and a carcinogenesis long-term animal study, we fed rats four different diets (control, chicken, beef, and blood sausage as a high heme diet). In a randomized crossover human study, four different diets were fed (a 60 g/d red meat baseline diet, 120 g/d red meat, baseline diet supplemented with heme iron, and baseline diet supplemented with nonheme iron). Results: DHN-MA excretion increased dramatically in rats fed high heme diets, and the excretion paralleled the number of preneoplastic lesions in azoxymethane initiated rats (P < 0.0001). In the human study, the heme supplemented diet resulted in a 2-fold increase in DHN-MA (P < 0.001). Urinary 8-iso-PGF2A increased moderately in rats fed a high heme diet (P < 0.0001), but not in humans. Conclusion: Urinary DHN-MA is a useful noninvasive biomarker for determining the risk of preneoplastic lesions associated with heme iron consumption and should be further investigated as a potential biomarker of colon cancer risk. (
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Dihydroxynonene Mercapturic Acid, a urinary metabolite of 4-hydroxynonenal, as a biomarker of lipid peroxidation.
BioFactors, 2005Co-Authors: Géraldine Peiro, Jacques Alary, Jean Pierre Cravedi, Estelle Rathahao, Jean-paul Steghens, Françoise GuéraudAbstract:The objective of our study was to compare the information obtained through the use of three different urinary biomarkers of lipoperoxidation during the time course of a bromotrichloromethane (BrCCl3) induced oxidative stress in rats. These biomarkers were malondialdehyde (MDA) measured by LC/MS after derivatization, the isoprostane 8-iso-PGF2alpha measured by enzyme immunoassay and 1,4-dihydroxynonene Mercapturic Acid (DHN-MA), the major 4-hydroxynonenal urinary metabolite [1], measured by LC-MS. Male Wistar rats received a single dose of 100 microL/kg BrCCl3 per os and lipid peroxidation was estimated every day for a 4-day-period after treatment. MDA, 8-iso-PGF2alpha and DHN-MA significantly increased in response to BrCCl3 treatment for this period of time, and DHN-MA showed the main increase during the 24-48 h period after treatment.
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Liquid chromatography-multistage tandem mass spectrometry for the quantification of dihydroxynonene Mercapturic Acid (DHN-MA), a urinary end-metabolite of 4-hydroxynonenal
Analytical and Bioanalytical Chemistry, 2005Co-Authors: Estelle Rathahao, Jacques Alary, Françoise Guéraud, G Peiro, N Martins, Laurent DebrauwerAbstract:The Mercapturic Acid conjugate of 1,4-dihydroxynonene (DHN-MA) is a urinary metabolite of 4-hydroxynonenal (4-HNE), one of the main lipid peroxidation products occurring in vivo. To determine its level in urine, a combination of liquid chromatography with positive electrospray-multistage tandem mass spectrometry has been developed. A deuterated analog of the target compound (DHN-MA) with six deuterium atoms was synthesized and used as the internal standard. Three-stage tandem mass spectrometry was used, providing good selectivity for the detection of DHN-MA. The response of the system to DHN-MA was linear in the 5-100 ng range. Urine samples spiked with different levels of standard DHN-MA were used to evaluate the influence of matrix effects on the linearity. The repeatability of the method was also determined by using repeated 5 ng injections of DHN-MA, providing a RSD of 10%. The method was then applied to the determination of DHN-MA in rat urine samples; increased levels of urinary DHN-MA in urine from rats treated with BrCCl3 indicates that lipid peroxidation processes take place in such rats.
Yiping Ren - One of the best experts on this subject based on the ideXlab platform.
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metabolomics based biomarker analysis of dihydroxypropyl Mercapturic Acid isomers from 3 monochloropropane 1 2 diol and glycidol for evaluation of toxicokinetics in rats and daily internal exposure in humans
Talanta, 2019Co-Authors: Wei Jia, Xinyu Chen, Yiping Ren, Lei Mao, Hong Miao, Dawei Chen, Yu ZhangAbstract:Abstract 3-Monochloropropane-1,2-diol (3-MCPD), glycidol, and their esters are some major sources of risk factors during food processing. Here we showed the biomarker analysis of 2,3-dihydroxypropyl Mercapturic Acid (DHPMA) isomers which derived from the metabolism of 3-MCPD, glycidol, and their esters in urine of rats and humans. Iso-DHPMA, a novel urinary metabolite, was discovered and detected in urine of rats, which were orally administered with glycidol but not 3-MCPD. Using the quadrupole-orbitrap high-resolution mass spectrometry, we confirmed that iso-DHPMA appeared a specific biomarker which derived from glycidol. The limit of quantification (signal-to-noise ratio, 10:1) of the analytes in urine of rats and humans were 1.33 ng/mL and 1.56 ng/mL, respectively. Acceptable within-laboratory reproducibility (RSD
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toxicokinetics and internal exposure of acrylamide new insight into comprehensively profiling Mercapturic Acid metabolites as short term biomarkers in rats and chinese adolescents
Archives of Toxicology, 2017Co-Authors: Qiao Wang, Xinyu Chen, Yiping Ren, Qing Chen, Zhen Meng, Jun Cheng, Yunyan Zheng, Weijiang Zeng, Qingning Zhao, Yu ZhangAbstract:Acrylamide is classified as a probable carcinogen to humans and generated from Maillard reaction. Currently, the short-term exposure to acrylamide was evaluated via external diet sources in vitro or two main Mercapturic Acid metabolites: N-acetyl-S-(2-carbamoylethyl)-l-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-l-cysteine (GAMA) in vivo. In the present work, we comprehensively profiled four Mercapturic Acid metabolites and evaluated their internal exposure in rats and Chinese adolescents. The cumulative excretion of Mercapturic Acid metabolites contributes 38.4–73.0 and 43.8–63.6 % of total in vivo metabolites of acrylamide in male and female rats, respectively, when 1, 10, and 50 mg/kg bw of acrylamide were orally administered. Toxicokinetic study revealed that the conversion of acrylamide into glycidamide and glutathione coupling process is highly related to the gender and oral gavage dose via evaluating kinetic parameters, accumulative excretion percentages, and molar ratios of oxidative to reductive metabolism. In human study, a total of 101 Chinese adolescents (41 men and 60 women) were enrolled and served with a meal of potato chips, corresponding to a single-dose (12.6 μg/kg bw) exposure to acrylamide. Toxicokinetic work showed that AAMA is an early and predominant metabolite appearing as a biomarker in urine. N-acetyl-S-(2-carbamoylethyl)-l-cysteine-sulfoxide (AAMA-sul), an oxidative product from AAMA, exhibits a higher peak concentration than GAMA and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-l-cysteine (iso-GAMA) during the whole 48-h toxicokinetic period. The internal exposure via four Mercapturic Acid metabolites is associated with the gender and body mass index characteristics. Thus, current study aims at Mercapturic Acid metabolites as urinary biomarkers and provides comprehensive insights into the short-term internal exposure to acrylamide.
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comprehensive profiling of Mercapturic Acid metabolites from dietary acrylamide as short term exposure biomarkers for evaluation of toxicokinetics in rats and daily internal exposure in humans using isotope dilution ultra high performance liquid chro
Analytica Chimica Acta, 2015Co-Authors: Yu Zhang, Qiao Wang, Jun Cheng, Jingshun Zhang, Yiping RenAbstract:Mercapturic Acid metabolites from dietary acrylamide are important short-term exposure biomarkers for evaluating the in vivo toxicity of acrylamide. Most of studies have focused on the measurement of two metabolites, N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA). Thus, the comprehensive profile of acrylamide urinary metabolites cannot be fully understood. We developed an isotope dilution ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous determination of all four Mercapturic Acid adducts of acrylamide and its primary metabolite glycidamide under the electroscopy ionization negative (ESI-) mode in the present study. The limit of detection (LOD) and limit of quantification (LOQ) of the analytes ranged 0.1-0.3 ng/mL and 0.4-1.0 ng/mL, respectively. The recovery rates with low, intermediate and high spiking levels were calculated as 95.5%-105.4%, 98.2%-114.0% and 92.2%-108.9%, respectively. Acceptable within-laboratory reproducibility (RSD<7.0%) substantially supported the use of current method for robust analysis. Rapid pretreatment procedures and short run time (8 min per sample) ensured good efficiency of metabolism profiling, indicating a wide application for investigating short-term internal exposure of dietary acrylamide. Our proposed UHPLC-MS/MS method was successfully applied to the toxicokinetic study of acrylamide in rats. Meanwhile, results of human urine analysis indicated that the levels of N-acetyl-S-(2-carbamoylethyl)-L-cysteine-sulfoxide (AAMA-sul), which did not appear in the Mercapturic Acid metabolites in rodents, were more than the sum of GAMA and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (iso-GAMA). Thus, AAMA-sul may alternatively become a specific biomarker for investigating the acrylamide exposure in humans. Current proposed method provides a substantial methodology support for comprehensive profiling of toxicokinetics and daily internal exposure evaluations of acrylamide in vivo.