ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2012
P2X7 receptor-mediated purinergic signaling promotes liver injury in acetaminophen hepatotoxicity in mice.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 135 citations in OpenAlex.
- Neutrophil-T cell cross talk in noninfectious liver diseases.American journal of physiology. Gastrointestinal and liver physiology · 2026Review
- NLRP3 inflammasome: structure, mechanism, drug-induced organ toxicity, therapeutic strategies, and future perspectives.RSC medicinal chemistry · 2025Review
- Unveiling the nexus: pyroptosis and its crucial implications in liver diseases.Molecular and cellular biochemistry · 2025Review
- Purinergic signaling and cholangiocyte regeneration: a new frontier in ischemic liver injury.Frontiers in transplantation · 2025Review
- Purinergic Signaling in Non-Parenchymal Liver Cells.International journal of molecular sciences · 2024Review
- The Role of Mechanistic Biomarkers in Understanding Acetaminophen Hepatotoxicity in Humans.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- Salivary metabolites are promising noninvasive biomarkers of drug-induced liver injury.World journal of gastroenterology · 2024Article
- Serine synthesis via reversed SHMT2 activity drives glycine depletion and acetaminophen hepatotoxicity in MASLD.Cell metabolism · 2024Article
- Extracellular Vesicles in Hepatobiliary Health and Disease.Comprehensive Physiology · 2023Review
- Review
- Mitigation of acetaminophen-induced liver toxicity by the novel phosphatidylinositol 3-kinase inhibitor alpelisib.Frontiers in pharmacology · 2023Article
- P2X7 Receptor in Alcoholic Steatohepatitis and Alcoholic Liver Fibrosis.Journal of clinical and translational hepatology · 2022Review
- Article
- Generation of pro-and anti-inflammatory mediators after acetaminophen overdose in surviving and non-surviving patients.Toxicology letters · 2022Article
- Sapidolide A alleviates acetaminophen-induced acute liver injury by inhibiting NLRP3 inflammasome activation in macrophages.Acta pharmacologica Sinica · 2022Article
- Review
- Targeting ectonucleotidases to treat inflammation and halt cancer development in the gut.Biochemical pharmacology · 2021Review
- Clodronate, an inhibitor of the vesicular nucleotide transporter, ameliorates steatohepatitis and acute liver injury.Scientific reports · 2021Article
- Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities.Cellular & molecular immunology · 2021Review
- Pathophysiological Role of Purinergic P2X Receptors in Digestive System Diseases.Frontiers in physiology · 2021Review
21 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Inflammation contributes to liver injury in acetaminophen (APAP) hepatotoxicity in mice and is triggered by stimulation of immune cells. The purinergic receptor P2X7 is upstream of the nod-like receptor family, pryin domain containing-3 (NLRP3) inflammasome in immune cells and is activated by ATP and NAD that serve as damage-associated molecular patterns. APAP hepatotoxicity was assessed in mice genetically deficient in P2X7, the key inflammatory receptor for nucleotides (P2X7-/-), and in wild-type mice. P2X7-/- mice had significantly decreased APAP-induced liver necrosis. In addition, APAP-poisoned mice were treated with the specific P2X7 antagonist A438079 or etheno-NAD, a competitive antagonist of NAD. Pre- or posttreatment with A438079 significantly decreased APAP-induced necrosis and hemorrhage in APAP liver injury in wild-type but not P2X7-/- mice. Pretreatment with etheno-NAD also significantly decreased APAP-induced necrosis and hemorrhage in APAP liver injury. In addition, APAP toxicity in mice lacking the plasma membrane ecto-NTPDase CD39 (CD39-/-) that metabolizes ATP was examined in parallel with the use of soluble apyrase to deplete extracellular ATP in wild-type mice. CD39-/- mice had increased APAP-induced hemorrhage and mortality, whereas apyrase also decreased APAP-induced mortality. Kupffer cells were treated with extracellular ATP to assess P2X7-dependent inflammasome activation. P2X7 was required for ATP-stimulated IL-1β release. In conclusion, P2X7 and exposure to the ligands ATP and NAD are required for manifestations of APAP-induced hepatotoxicity.
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