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High-resolution mas...
High-resolution mass spectrometry identifies delayed biomarkers for improved precision in acetaminophen/paracetamol human biomonitoring
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- Gorrochategui, Eva (författare)
- EHESP French School of Public Health
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- Le Vee, Marc (författare)
- EHESP French School of Public Health
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- Selmi, Habiba (författare)
- EHESP French School of Public Health
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- Gérard, Anne (författare)
- EHESP French School of Public Health
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- Chaker, Jade (författare)
- EHESP French School of Public Health
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- Krais, Annette M. (författare)
- Lund University,Lunds universitet,Tillämpad masspektrometri inom miljömedicin,Forskargrupper vid Lunds universitet,Centrum för hälsosamma inomhusmiljöer, CHIE,Annan verksamhet, LTH,Lunds Tekniska Högskola,LTH profilområde: Aerosoler,LTH profilområden,Applied Mass Spectrometry in Environmental Medicine,Lund University Research Groups,Centre for Healthy Indoor Environments,Other operations, LTH,Faculty of Engineering, LTH,LTH Profile Area: Aerosols,LTH Profile areas,Faculty of Engineering, LTH
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- Lindh, Christian (författare)
- Lund University,Lunds universitet,Tillämpad masspektrometri inom miljömedicin,Forskargrupper vid Lunds universitet,Applied Mass Spectrometry in Environmental Medicine,Lund University Research Groups
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- Fardel, Olivier (författare)
- EHESP French School of Public Health
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- Chevrier, Cécile (författare)
- EHESP French School of Public Health
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- Le Cann, Pierre (författare)
- EHESP French School of Public Health
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- Miller, Gary W. (författare)
- Columbia University
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- Barouki, Robert (författare)
- Paris Descartes University
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- Jégou, Bernard (författare)
- EHESP French School of Public Health
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- Gicquel, Thomas (författare)
- University of Rennes I
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- Kristensen, David M. (författare)
- Roskilde University,Copenhagen University Hospital,University of Copenhagen,EHESP French School of Public Health
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- David, Arthur (författare)
- EHESP French School of Public Health
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(creator_code:org_t)
- 2023
- 2023
- Engelska.
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Ingår i: Environment International. - 0160-4120. ; 181
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Paracetamol/acetaminophen (N-acetyl-p-aminophenol, APAP) is a top selling analgesic used in more than 600 prescription and non-prescription pharmaceuticals. To study efficiently some of the potential undesirable effects associated with increasing APAP consumption (e.g., developmental disorders, drug-induced liver injury), there is a need to improve current APAP biomonitoring methods that are limited by APAP short half-life. Here, we demonstrate using high-resolution mass spectrometry (HRMS) in several human studies that APAP thiomethyl metabolite conjugates (S-methyl-3-thioacetaminophen sulfate and S-methyl-3-thioacetaminophen sulphoxide sulfate) are stable biomarkers with delayed excretion rates compared to conventional APAP metabolites, that could provide a more reliable history of APAP ingestion in epidemiological studies. We also show that these biomarkers could serve as relevant clinical markers to diagnose APAP acute intoxication in overdosed patients, when free APAP have nearly disappeared from blood. Using in vitro liver models (HepaRG cells and primary human hepatocytes), we then confirm that these thiomethyl metabolites are directly linked to the toxic N-acetyl-p-benzoquinone imine (NAPQI) elimination, and produced via an overlooked pathway called the thiomethyl shunt pathway. Further studies will be needed to determine whether the production of the reactive hepatotoxic NAPQI metabolites is currently underestimated in human. Nevertheless, these biomarkers could already serve to improve APAP human biomonitoring, and investigate, for instance, inter-individual variability in NAPQI production to study underlying causes involved in APAP-induced hepatotoxicity. Overall, our findings demonstrate the potential of exposomics-based HRMS approach to advance towards a better precision for human biomonitoring.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Public Health, Global Health, Social Medicine and Epidemiology (hsv//eng)
Nyckelord
- Acetaminophen/paracetamol
- Chemical exposome
- Exposomics
- High-resolution mass spectrometry
- Human biomonitoring
- Thiomethyl metabolites
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Gorrochategui, E ...
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Le Vee, Marc
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Selmi, Habiba
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Gérard, Anne
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Chaker, Jade
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Krais, Annette M ...
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visa fler...
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Lindh, Christian
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Fardel, Olivier
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Chevrier, Cécile
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Le Cann, Pierre
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Miller, Gary W.
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Barouki, Robert
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Jégou, Bernard
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Gicquel, Thomas
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Kristensen, Davi ...
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David, Arthur
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visa färre...
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