ArticleToxicological sciences : an official journal of the Society of Toxicology2010
Protective and damaging effects of platelets in acute cholestatic liver injury revealed by depletion and inhibition strategies.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2010. 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, 51 citations in OpenAlex.
- Liver Fibrosis and Purinergic Signaling: Autocrine-Paracrine Role of ATP in Liver Damage.International journal of molecular sciences · 2026Review
- Comparative proteomics reveals different protein expression in platelets in patients with alcoholic liver cirrhosis.Proteome science · 2024Article
- Chronic Stress and Gonadectomy Affect the Expression of Cx37, Cx40 and Cx43 in the Spinal Cord.Life (Basel, Switzerland) · 2021Article
- Von Willebrand factor exerts hepatoprotective effects in acute but not chronic cholestatic liver injury in mice.Toxicology · 2021Article
- Targeting von Willebrand factor in liver diseases: A novel therapeutic strategy?Journal of thrombosis and haemostasis : JTH · 2021Review
- Till Death Do Us Part-The Multifaceted Role of Platelets in Liver Diseases.International journal of molecular sciences · 2021Review
- Platelets in chronic liver disease, from bench to bedside.JHEP reports : innovation in hepatology · 2019Review
- Platelets and Platelet-Derived Extracellular Vesicles in Liver Physiology and Disease.Hepatology communications · 2019Review
- Platelets as Modulators of Liver Diseases.Seminars in thrombosis and hemostasis · 2018Review
- Platelet-neutrophil interactions as drivers of inflammatory and thrombotic disease.Cell and tissue research · 2018Review
- Platelets: No longer bystanders in liver disease.Hepatology (Baltimore, Md.) · 2016Review
- Article
- Role of Fibrin(ogen) in Progression of Liver Disease: Guilt by Association?Seminars in thrombosis and hemostasis · 2016Review
- [Clinical features of different clinical forms of childhood congenital hepatic fibrosis].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2016Article
- Platelets and protease-activated receptor-4 contribute to acetaminophen-induced liver injury in mice.Blood · 2015Article
- An Endocrine Genetic Signal Between Blood Cells and Vascular Smooth Muscle Cells: Role of MicroRNA-223 in Smooth Muscle Function and Atherogenesis.Journal of the American College of Cardiology · 2015Article
- Platelets are relevant mediators of renal injury induced by primary endothelial lesions.American journal of physiology. Renal physiology · 2015Article
- Coagulation-driven platelet activation reduces cholestatic liver injury and fibrosis in mice.Journal of thrombosis and haemostasis : JTH · 2015Article
- Hepatic sinusoidal endothelium avidly binds platelets in an integrin-dependent manner, leading to platelet and endothelial activation and leukocyte recruitment.American journal of physiology. Gastrointestinal and liver physiology · 2013Article
- Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Alpha-naphthylisothiocyanate (ANIT) causes cholestatic hepatitis characterized by intrahepatic bile duct epithelial cell injury and periportal hepatocellular necrosis. The progression of ANIT-induced hepatocyte injury is reported to involve extrahepatic cells including platelets. We showed recently that the procoagulant protein tissue factor (TF) is essential for ANIT-induced coagulation and contributes to ANIT-induced liver necrosis. Platelets have been shown to express TF and can contribute to coagulation cascade activation. To this end, we tested the hypothesis that platelet-dependent coagulation contributes to ANIT-induced liver injury. In ANIT (60 mg/kg)-treated mice, activation of the coagulation cascade occurred prior to a decrease of platelets in the blood. Immunostaining for glycoprotein IIb (CD41) revealed platelet accumulation along the borders of necrotic foci in livers of ANIT-treated mice. Antibody-mediated platelet depletion did not affect coagulation but markedly affected liver histopathology in ANIT-treated mice. Platelet depletion induced marked pooling of blood within necrotic lesions consistent with parenchymal-type peliosis as early as 24 h after ANIT treatment. In contrast, treatment with the P2Y(12) inhibitor clopidogrel significantly reduced ANIT-induced hepatocyte necrosis and serum alanine aminotransferase activity but did not exaggerate bleeding into necrotic foci. Clopidogrel also reduced hepatic neutrophil accumulation but did not affect induction of Intercellular adhesion molecule-1 or chemokine CxC motif ligand-1 messenger RNA expression in liver. The data indicate that ANIT-induced coagulation is platelet independent and that platelets contribute to ANIT-induced hepatocyte necrosis by promoting neutrophil accumulation. In contrast, severe thrombocytopenia induces parenchymal-type peliosis in the livers of ANIT-treated mice, a rare hepatic lesion associated with pooling of blood in the liver.
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Registered trials
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.