ArticleToxicology letters2019
Role of extracellular vesicles in release of protein adducts after acetaminophen-induced liver injury in mice and humans.
Article in Toxicology letters, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
13 citing papers in PubMed, 30 citations in OpenAlex.
- SPECTRA-based Detection of Drug-Induced Hepatotoxicity through Extracellular Vesicle Analysis.Sensors and actuators. B, Chemical · 2026Article
- NAPQI is absent in the mouse brain after sub-hepatotoxic and hepatotoxic doses of acetaminophen.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- SHINE: SERS-based Hepatotoxicity detection using Inference from Nanoscale Extracellular vesicle content.bioRxiv : the preprint server for biology · 2025Article
- The Role of Mechanistic Biomarkers in Understanding Acetaminophen Hepatotoxicity in Humans.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- Emergence of Extracellular Vesicles as "Liquid Biopsy" for Neurological Disorders: Boom or Bust.Pharmacological reviews · 2024Review
- Acetaminophen Hepatotoxicity: Paradigm for Understanding Mechanisms of Drug-Induced Liver Injury.Annual review of pathology · 2024Review
- The therapeutic potential of exosomes derived from different cell sources in liver diseases.American journal of physiology. Gastrointestinal and liver physiology · 2022Review
- Biomarkers of drug-induced liver injury: a mechanistic perspective through acetaminophen hepatotoxicity.Expert review of gastroenterology & hepatology · 2021Review
- Extracellular vesicles: Roles and applications in drug-induced liver injury.Advances in clinical chemistry · 2021Review
- Apigenin Attenuates Acetaminophen-Induced Hepatotoxicity by Activating AMP-Activated Protein Kinase/Carnitine Palmitoyltransferase I Pathway.Frontiers in pharmacology · 2020Article
- Acetaminophen Protein Adducts in Hospitalized Children Receiving Multiple Doses of Acetaminophen.Journal of clinical pharmacology · 2019Observational
- Propagation of Pericentral Necrosis During Acetaminophen-Induced Liver Injury: Evidence for Early Interhepatocyte Communication and Information Exchange.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Biomarkers of drug-induced liver injury.Advances in pharmacology (San Diego, Calif.) · 2019Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Formation of acetaminophen (APAP) protein adducts are a critical feature of APAP hepatotoxicity, and circulating protein adducts have recently been utilized in bioassays for identification of APAP overdose in humans. Despite their clinical significance, mechanisms of adduct release into the circulation are not well understood. Extracellular vesicles (EVs) are discrete membrane bound vesicles, which package cellular cargo and function in extracellular transport. Clarification of their role in transport of APAP adducts is relevant since adduct packaging within these vesicles could shield them from detection by antibody based methods, resulting in under-estimating adduct levels. Hence, this study evaluated EV release after APAP overdose in primary mouse hepatocytes and human HepaRG cells in vitro, in mice and APAP overdose patients in vivo and examined their role in transport of APAP-protein adducts. EVs were characterized by size and protein composition and the levels of APAP-protein adducts were measured. Significant elevations in circulating EV numbers were observed 6 h after APAP overdose in vivo and by 4 h in primary mouse hepatocytes in culture. EVs were also elevated in media from HepaRG cells by 24 h after APAP exposure, an effect recapitulated in APAP overdose patients, where EV numbers were elevated compared to healthy controls. Although APAP-protein adducts were elevated in circulation and media parallel to the increased exosome release, no detectable adducts were observed within EVs. This suggests that although APAP overdose enhances EV release from hepatocytes in mice and humans, it is not a significant mechanism of release of APAP protein adducts into circulation.
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