ArticleScientific reports2017
Low-dose acetaminophen induces early disruption of cell-cell tight junctions in human hepatic cells and mouse liver.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
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- Transcriptomic signature, bioactivity and safety of a non-hepatotoxic analgesic generating AM404 in the midbrain PAG region.Scientific reports · 2024Article
- Metabolism of Acetaminophen by Enteric Epithelial Cells Mitigates Hepatocellular Toxicity In Vitro.Journal of clinical medicine · 2023Article
- Effects of acute and chronic disease on cell junctions in mouse liver.EXCLI journal · 2023Article
- Interruption of bile acid uptake by hepatocytes after acetaminophen overdose ameliorates hepatotoxicity.Journal of hepatology · 2022Article
- Genetic and pharmacological inhibition of XBP1 protects against APAP hepatotoxicity through the activation of autophagy.Cell death & disease · 2022Article
- FuSe: a tool to move RNA-Seq analyses from chromosomal/gene loci to functional grouping of mRNA transcripts.Bioinformatics (Oxford, England) · 2021Article
- Establishment of a novel hepatitis B virus culture system using immortalized human hepatocytes.Scientific reports · 2020Article
- A novel pipeline of 2-(benzenesulfonamide)-N-(4-hydroxyphenyl) acetamide analgesics that lack hepatotoxicity and retain antipyresis.European journal of medicinal chemistry · 2020Article
- Contrasting model mechanisms of alanine aminotransferase (ALT) release from damaged and necrotic hepatocytes as an example of general biomarker mechanisms.PLoS computational biology · 2020Article
- Mitochondrial depolarization and repolarization in the early stages of acetaminophen hepatotoxicity in mice.Toxicology · 2020Article
- Article
- Probiotic Bacillus Spores Protect Against Acetaminophen Induced Acute Liver Injury in Rats.Nutrients · 2020Article
- The MicroRNA-based Liquid Biopsy Improves Early Assessment of Lethal Acetaminophen Poisoning: A Case Report.The American journal of case reports · 2020Article
- Biosensors for Studies on Adhesion-Mediated Cellular Responses to Their Microenvironment.Frontiers in bioengineering and biotechnology · 2020Review
- Application of Impedance-Based Techniques in Hepatology Research.Journal of clinical medicine · 2019Review
- Blood-Bile Barrier: Morphology, Regulation, and Pathophysiology.Gene expression · 2019Review
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 2 countries.
Funding
Abstract
Dysfunction of cell-cell tight junction (TJ) adhesions is a major feature in the pathogenesis of various diseases. Liver TJs preserve cellular polarity by delimiting functional bile-canalicular structures, forming the blood-biliary barrier. In acetaminophen-hepatotoxicity, the mechanism by which tissue cohesion and polarity are affected remains unclear. Here, we demonstrate that acetaminophen, even at low-dose, disrupts the integrity of TJ and cell-matrix adhesions, with indicators of cellular stress with liver injury in the human hepatic HepaRG cell line, and primary hepatocytes. In mouse liver, at human-equivalence (therapeutic) doses, dose-dependent loss of intercellular hepatic TJ-associated ZO-1 protein expression was evident with progressive clinical signs of liver injury. Temporal, dose-dependent and specific disruption of the TJ-associated ZO-1 and cytoskeletal-F-actin proteins, correlated with modulation of hepatic ultrastructure. Real-time impedance biosensing verified in vitro early, dose-dependent quantitative decreases in TJ and cell-substrate adhesions. Whereas treatment with NAPQI, the reactive metabolite of acetaminophen, or the PKCα-activator and TJ-disruptor phorbol-12-myristate-13-acetate, similarly reduced TJ integrity, which may implicate oxidative stress and the PKC pathway in TJ destabilization. These findings are relevant to the clinical presentation of acetaminophen-hepatotoxicity and may inform future mechanistic studies to identify specific molecular targets and pathways that may be altered in acetaminophen-induced hepatic depolarization.
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