ArticleCell proliferation2018
Replicative stress and alterations in cell cycle checkpoint controls following acetaminophen hepatotoxicity restrict liver regeneration.
Article in Cell proliferation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
The trial behind it
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Bi-allelic WDHD1 variants cause microcephalic primordial dwarfism.American journal of human genetics · 2026Article
- Ataxia-telangiectasia mutated activation mediates transforming growth factor beta signaling in acetaminophen-induced liver injury in mice.Physiological reports · 2025Article
- Silibinin alleviates acute liver failure by modulating AKT/GSK3β/Nrf2/GPX4 pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Novel Optical Criteria and Mechanisms of Critical Decline in Liver Regenerative Potential.Cells · 2024Article
- Liver regeneration after injury: Mechanisms, cellular interactions and therapeutic innovations.Clinical and translational medicine · 2024Review
- EGR1 is crucial for the chlorogenic acid-provided promotion on liver regeneration and repair after APAP-induced liver injury.Cell biology and toxicology · 2023Article
- The Ploidy State as a Determinant of Hepatocyte Proliferation.Seminars in liver disease · 2023Review
- Article
- Hepatocyte Transplantation Rebalances Cytokines for Hepatic Regeneration in Rats with Ataxia Telangiectasia Mutated Pathway-Related Acute Liver Failure.The American journal of pathology · 2023Article
- Unraveling the effect of intra- and intercellular processes on acetaminophen-induced liver injury.NPJ systems biology and applications · 2022Article
- Peroxiredoxin 3 Inhibits Acetaminophen-Induced Liver Pyroptosis Through the Regulation of Mitochondrial ROS.Frontiers in immunology · 2021Article
- Comparison of liver regeneration after partial hepatectomy and acetaminophen-induced acute liver failure: A global picture based on transcriptome analysis.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2020Article
- Ataxia telangiectasia mutated pathway disruption affects hepatic DNA and tissue damage in nonalcoholic fatty liver disease.Experimental and molecular pathology · 2020Article
- Cerium oxide nanoparticles improve liver regeneration after acetaminophen-induced liver injury and partial hepatectomy in rats.Journal of nanobiotechnology · 2019Article
- Decellularized bovine placentome for portacavally-interposed heterotopic liver transplantation in rats.Materials science & engineering. C, Materials for biological applications · 2019Article
- Liver Regeneration after Acetaminophen Hepatotoxicity: Mechanisms and Therapeutic Opportunities.The American journal of pathology · 2019Review
- Efficient Reconstitution of Hepatic Microvasculature by Endothelin Receptor Antagonism in Liver Sinusoidal Endothelial Cells.Human gene therapy · 2019Article
- Replicative stress and alterations in cell cycle checkpoint controls following acetaminophen hepatotoxicity restrict liver regeneration.Cell proliferation · 2018Article
- Hepatic differentiation of human pluripotent stem cells by developmental stage-related metabolomics products.Differentiation; research in biological diversityArticle
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
objectivesAcetaminophen hepatotoxicity is a leading cause of hepatic failure with impairments in liver regeneration producing significant mortality. Multiple intracellular events, including oxidative stress, mitochondrial damage, inflammation, etc., signify acetaminophen toxicity, although how these may alter cell cycle controls has been unknown and was studied for its significance in liver regeneration. MATERIALS AND
methodsAssays were performed in HuH-7 human hepatocellular carcinoma cells, primary human hepatocytes and tissue samples from people with acetaminophen-induced acute liver failure. Cellular oxidative stress, DNA damage and cell proliferation events were investigated by mitochondrial membrane potential assays, flow cytometry, fluorescence staining, comet assays and spotted arrays for protein expression after acetaminophen exposures.
resultsIn experimental groups with acetaminophen toxicity, impaired mitochondrial viability and substantial DNA damage were observed with rapid loss of cells in S and G2/M and cell cycle restrictions or even exit in the remainder. This resulted from altered expression of the DNA damage regulator, ATM and downstream transducers, which imposed G1/S checkpoint arrest, delayed entry into S and restricted G2 transit. Tissues from people with acute liver failure confirmed hepatic DNA damage and cell cycle-related lesions, including restrictions of hepatocytes in aneuploid states. Remarkably, treatment of cells with a cytoprotective cytokine reversed acetaminophen-induced restrictions to restore cycling.
conclusionsCell cycle lesions following mitochondrial and DNA damage led to failure of hepatic regeneration in acetaminophen toxicity but their reversibility offers molecular targets for treating acute liver failure.
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