ArticleArchives of toxicology2023
Dose-dependent pleiotropic role of neutrophils during acetaminophen-induced liver injury in male and female mice.
Article in Archives of toxicology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- Redefining senescence through hepatocyte fate changes in liver diseases.Trends in endocrinology and metabolism: TEM · 2026Review
- Differential effects on acetaminophen-induced nephrotoxicity and liver injury following modulation of glutathione resynthesis.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2026Article
- Hepatocyte-specific epidermal growth factor receptor (EGFR) deletion attenuates acetaminophen-induced liver injury in mice.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Widely Targeted Liver Metabolomics Reveals Potential Biomarkers in Mice with Drug-Induced Liver Injury.Metabolites · 2026Article
- The endothelial growth factor angiopoietin-2 is an accurate prognostic biomarker in patients with acetaminophen-induced acute liver failure.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Are New Approach Methodologies (NAMs) the Holy Grail of toxicology?Toxicological sciences : an official journal of the Society of Toxicology · 2025Review
- Platelets mediate neutrophil infiltration and exacerbate liver injury and sinusoidal endothelial cell damage after a severe acetaminophen overdose in mice.Archives of toxicology · 2025Article
- Mechanisms of drug induced liver injury.Cellular and molecular life sciences : CMLS · 2025Review
- Cryopreserved human alternatively activated macrophages promote resolution of acetaminophen-induced liver injury in mouse.NPJ Regenerative medicine · 2025Article
- The multiple mechanisms and modes of cell death after acetaminophen overdose.Exploration of digestive diseases · 2025Article
- Natural Products That Protect Against Acetaminophen Hepatotoxicity: A Call for Increased Rigor in Preclinical Studies of Dietary Supplements.Journal of dietary supplements · 2025Review
- Potential Biomarkers and Therapeutic Targets in Hepatitis B Virus-related Acute Liver Failure: Interplay of the Ferroptosis, Autophagy and Immune Responses.International journal of medical sciences · 2025Article
- The Role of Mechanistic Biomarkers in Understanding Acetaminophen Hepatotoxicity in Humans.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- Good Cells Go Bad: Immune Dysregulation in the Transition from Acute Liver Injury to Liver Failure After Acetaminophen Overdose.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- The p21Toxicology · 2024Article
- Myeloid-Mas Signaling Modulates Pathogenic Crosstalk among MYCAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Spatial analysis of renal acetaminophen metabolism and its modulation by 4-methylpyrazole with DESI mass spectrometry imaging.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Acetaminophen Hepatotoxicity: Paradigm for Understanding Mechanisms of Drug-Induced Liver Injury.Annual review of pathology · 2024Review
- Targeting cathepsin C ameliorates murine acetaminophen-induced liver injury.Theranostics · 2024Article
- Neutrophil-dependent hepatic platelet accumulation and liver injury revealed by acetaminophen dose-response studies.Research and practice in thrombosis and haemostasis · 2024Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Acetaminophen (APAP) overdose is the leading cause of acute liver failure in western countries. APAP can cause extensive hepatocellular necrosis, which triggers an inflammatory response involving neutrophil and monocyte recruitment. Particularly the role of neutrophils in the injury mechanism of APAP hepatotoxicity has been highly controversial. Thus, the objective of the current study was to assess whether a potential contribution of neutrophils was dependent on the APAP dose and the sex of the animals. Male and female C57BL/6 J mice were treated with 300 or 600 mg/kg APAP and the injury and inflammatory cell recruitment was evaluated between 6 and 48 h. In both male and female mice, ALT plasma levels and the areas of necrosis peaked at 12-24 h after both doses with more severe injury at the higher dose. In addition, Ly6g-positive neutrophils started to accumulate in the liver at 6 h and peaked at 6-12 h after 300 mg/kg and 12-24 h after 600 mg/kg for both sexes; however, the absolute numbers of hepatic neutrophils in the liver were significantly higher after the 600 mg/kg dose. Neutrophil infiltration correlated with mRNA levels of the neutrophil chemoattractant Cxcl2 in the liver. Treating mice with an anti-Cxcl2 antibody at 2 h after APAP significantly reduced neutrophil accumulation at 24 h after both doses and in both sexes. However, the injury was significantly reduced only after the high overdose. Thus, neutrophils, recruited through Cxcl2, have no effect on APAP-induced liver injury after 300 mg/kg but aggravate the injury only after severe overdoses.
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