ArticleToxicological sciences : an official journal of the Society of Toxicology2016
Subtoxic Alterations in Hepatocyte-Derived Exosomes: An Early Step in Drug-Induced Liver Injury?
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 76 citations in OpenAlex.
- SPECTRA-based Detection of Drug-Induced Hepatotoxicity through Extracellular Vesicle Analysis.Sensors and actuators. B, Chemical · 2026Article
- Tissue-Specific Extracellular Vesicles Enriched From Circulation: Exploring the Liquid Biopsy Perspective.Journal of extracellular biology · 2026Review
- Harnessing brain-derived extracellular vesicles to support RDoC-based drug development.Neuroscience applied · 2025Review
- The potential role of extracellular vesicles as hepatic diagnostic and therapeutic tools: Can the dream come true?iLIVER · 2024Review
- Roadmap to DILI research in Europe. A proposal from COST action ProEuroDILINet.Pharmacological research · 2024Article
- Possible Role of Extracellular Vesicles in Hepatotoxicity of Acetaminophen.International journal of molecular sciences · 2022Article
- Extracellular vesicles as mediators and markers of acute organ injury: current concepts.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2022Review
- Nucleic acids and proteins carried by exosomes from various sources: Potential role in liver diseases.Frontiers in physiology · 2022Review
- Extracellular vesicles in inflammation: Focus on the microRNA cargo of EVs in modulation of liver diseases.Journal of leukocyte biology · 2022Review
- Preclinical models of idiosyncratic drug-induced liver injury (iDILI): Moving towards prediction.Acta pharmaceutica Sinica. B · 2021Review
- Extracellular vesicles: mediators of intercellular communication in tissue injury and disease.Cell communication and signaling : CCS · 2021Review
- Mechanism of idiosyncratic drug induced liver injury (DILI): unresolved basic issues.Annals of translational medicine · 2021Review
- Methodological considerations for measuring biofluid-based microRNA biomarkers.Critical reviews in toxicology · 2021Article
- Advances on liver cell-derived exosomes in liver diseases.Journal of cellular and molecular medicine · 2021Review
- The Immunological Mechanisms and Immune-Based Biomarkers of Drug-Induced Liver Injury.Frontiers in pharmacology · 2021Review
- Extracellular vesicles: Roles and applications in drug-induced liver injury.Advances in clinical chemistry · 2021Review
- Pregnancy-Related Hormones Increase Nifedipine Metabolism in Human Hepatocytes by Inducing CYP3A4 Expression.Journal of pharmaceutical sciences · 2021Article
- Article
- Hepatocyte-Derived Exosomes Promote Liver Immune Tolerance: Possible Implications for Idiosyncratic Drug-Induced Liver Injury.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Intercellular Communication between Hepatic Cells in Liver Diseases.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Drug-induced liver injury (DILI) is a significant clinical and economic problem in the United States, yet the mechanisms that underlie DILI remain poorly understood. Recent evidence suggests that signaling molecules released by stressed hepatocytes can trigger immune responses that may be common across DILI mechanisms. Extracellular vesicles released by hepatocytes, principally hepatocyte-derived exosomes (HDEs), may constitute one such signal. To examine HDE alterations as a function of drug-induced stress, this work utilized prototypical hepatotoxicant acetaminophen (APAP) in male Sprague-Dawley (SD) rats, SD rat hepatocytes, and primary human hepatocytes. HDE were isolated using ExoQuick precipitation reagent and analyzed by quantification of the liver-specific RNAs albumin and microRNA-122 (miR-122). In vivo, significant elevations in circulating exosomal albumin mRNA were observed at subtoxic APAP exposures. Significant increases in exosomal albumin mRNA were also observed in primary rat hepatocytes at subtoxic APAP concentrations. In primary human hepatocytes, APAP elicited increases in both exosomal albumin mRNA and exosomal miR-122 without overt cytotoxicity. However, the number of HDE produced in vitro in response to APAP did not increase with exosomal RNA quantity. We conclude that significant drug-induced alterations in the liver-specific RNA content of HDE occur at subtoxic APAP exposures in vivo and in vitro, and that these changes appear to reflect selective packaging rather than changes in exosome number. The current findings demonstrate that translationally relevant HDE alterations occur in the absence of overt hepatocellular toxicity, and support the hypothesis that HDE released by stressed hepatocytes may mediate early immune responses in DILI.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.