ArticleBiochemical pharmacology2010
Susceptibility to acetaminophen (APAP) toxicity unexpectedly is decreased during acute viral hepatitis in mice.
Article in Biochemical pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- Antimicrobial potentials and challenges of paracetamol: A comprehensive reassessment based on database reports.Pharmaceutical science advances · 2025Review
- CMD-OPT model enables the discovery of a potent and selective RIPK2 inhibitor as preclinical candidate for the treatment of acute liver injury.Acta pharmaceutica Sinica. B · 2025Article
- Drug-Induced Liver Injury in Patients With Chronic Liver Disease.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Acetaminophen Protein Adducts in Hospitalized Children Receiving Multiple Doses of Acetaminophen.Journal of clinical pharmacology · 2019Observational
- Hepatoprotective Effect of Baicalein Against Acetaminophen-Induced Acute Liver Injury in Mice.Molecules (Basel, Switzerland) · 2018Article
- The Role of Cytochromes P450 in Infection.Frontiers in immunology · 2018Review
- The Synthetic Triterpenoid RTA 405 (CDDO-EA) Halts Progression of Liver Fibrosis and Reduces Hepatocellular Carcinoma Size Resulting in Increased Survival in an Experimental Model of Chronic Liver Injury.Toxicological sciences : an official journal of the Society of Toxicology · 2016Article
- Hepatitis C virus structural proteins can exacerbate or ameliorate acetaminophen-induced liver injury in mice.Archives of toxicology · 2015Article
- Chronic Deletion and Acute Knockdown of Parkin Have Differential Responses to Acetaminophen-induced Mitophagy and Liver Injury in Mice.The Journal of biological chemistry · 2015Article
- The role of intrahepatic CD3+/CD4-/CD8- double negative T (DN T) cells in enhanced acetaminophen toxicity.Toxicology and applied pharmacology · 2014Article
- Outcomes of patients with acetaminophen-associated toxic hepatitis at a far east poison center.SpringerPlus · 2013Article
- Acetaminophen hepatotoxicity and repair: the role of sterile inflammation and innate immunity.Liver international : official journal of the International Association for the Study of the Liver · 2012Review
- c-Jun N-terminal kinase (JNK)-dependent acute liver injury from acetaminophen or tumor necrosis factor (TNF) requires mitochondrial Sab protein expression in mice.The Journal of biological chemistry · 2011Article
- Polyinosinic-polycytidylic acid suppresses acetaminophen-induced hepatotoxicity independent of type I interferons and toll-like receptor 3.Hepatology (Baltimore, Md.) · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Acetaminophen (APAP) hepatotoxicity results from cytochrome P450 metabolism of APAP to the toxic metabolite, n-acetyl-benzoquinone imine (NAPQI), which reacts with cysteinyl residues to form APAP adducts and initiates cell injury. As APAP is commonly used during viral illnesses there has been concern that APAP injury may be additive to that of viral hepatitis, leading physicians to advise against its use in such patients; this has not been investigated experimentally. We infected C57BL/6 male mice with replication-deficient adenovirus to produce moderately severe acute viral hepatitis and observed that APAP doses that were hepatotoxic or lethal in control mice produced neither death nor additional increase in serum ALT when administered to infected mice at the peak of virus-induced liver injury. Moreover, the concentration of hepatic APAP-protein adducts formed in these mice was only 10% that in control mice. Protection from APAP hepatotoxicity also was observed earlier in the course of infection, prior to the peak virus-induced ALT rise. Hepatic glutathione limits APAP-protein adduct formation but glutathione levels were similar in control and infected mice. Cyp1a2 (E.C. 1.14.14.1) and Cyp2e1 (E.C. 1.14.13.n7) mRNA expression decreased by 3 days post-infection and hepatic Cyp2e1 protein levels were reduced almost 90% at 7 days, when adduct formation was maximally inhibited. In vitro, hepatocytes from virally infected mice also were resistant to APAP-induced injury but sensitive to NAPQI. Rather than potentiating APAP-induced liver injury, acute viral hepatitis in this model resulted in selective down-regulation of APAP metabolizing P450s in liver and decreased the risk of APAP hepatotoxicity.
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Registered trials
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