Acetaminophen-protein adducts are biomarkers of acetaminophen toxicity present in the centrilobular region of the liver of laboratory animals following the administration of toxic doses of acetaminophen. These biomarkers are highly specific for acetaminophen-induced hepatic injury and correlate with hepatic transaminase elevation. The objective of this prospective, multicenter study was to evaluate the clinical application of the measurement of acetaminophen-protein adducts in pediatric acetaminophen overdose patients. Serum samples were obtained from 51 children and adolescents with acetaminophen overdose at the time of routine blood sampling for clinical monitoring. Six subjects developed "severe" hepatotoxicity (transaminase elevation > 1,000 IU/L), and 6 subjects had transaminase elevation of 100 to 1,000 IU/L. Acetaminophen-protein adducts were detected in the serum of only 1 study subject, a patient with marked transaminase elevation (> 6,000 IU/L) and high risk for the development of hepatotoxicity according to the Rumack nomogram. While this study provides further support for the occurrence of covalent binding of acetaminophen to hepatic protein in humans following acetaminophen overdose, the detection of acetaminophen-protein adducts in serum with the current methodology requires significant biochemical evidence of hepatocellular injury.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1177/00912700122010744 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Targeting Autophagy for Acetaminophen-Induced Liver Injury: An Update.
Livers
September 2024
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Acetaminophen (APAP) overdose can induce hepatocyte necrosis and acute liver failure in experimental rodents and humans. APAP is mainly metabolized via hepatic cytochrome P450 enzymes to generate the highly reactive metabolite -acetyl--benzoquinone imine (NAPQI), which forms acetaminophen protein adducts (APAP-adducts) and damages mitochondria, triggering necrosis. APAP-adducts and damaged mitochondria can be selectively removed by autophagy.
View Article and Find Full Text PDFAdducts Post Acetaminophen Overdose Treated with a 12-Hour vs 20-Hour Acetylcysteine Infusion.
J Med Toxicol
April 2020
Departments of Emergency Medicine, and of Biomedical & Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
Introduction: Acetaminophen protein adducts in the circulation are a specific biomarker of acetaminophen oxidation, and may be a more sensitive measure of impending hepatic injury following overdose than alanine transaminase (ALT). We performed an exploratory analytical substudy of adducts during a clinical trial (NACSTOP) of abbreviated (12-hour) versus control (20-hour) acetylcysteine to identify any signal of diminished antidotal effectiveness with shortened therapy.
Methods: We measured adducts at 0, 12, and 20 hours from a convenience sample of subjects enrolled in the cluster-controlled NACSTOP trial evaluating a 12-hour ("abbreviated"; 200 mg/kg over 4 hours, 50 mg/kg over 8 hours) vs 20-hour acetylcysteine regimen ("control"; 200 mg/kg over 4 hours, 100 mg/kg over 16 hours).
Acute Liver Failure of unclear cause? Acetaminophen-protein adducts make the diagnosis.
Toxicol Commun
February 2020
Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital Research Institute, Little Rock, AR, USA.
Acetaminophen poisoning remains a leading cause of acute liver failure. Some cases may be difficult to diagnose when clinical findings are equivocal, the patient's history is misleading or incomplete, or the acetaminophen concentration is low or undetectable at arrival to care. We describe a case of a medically complicated young child whose acute liver failure had two of these features.
View Article and Find Full Text PDFPopulation Pharmacokinetic Modeling of Acetaminophen Protein Adducts in Adults and Children.
J Clin Pharmacol
May 2020
Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, University of Florida, Orlando, Florida, USA.
Acetaminophen protein adducts (adducts) are a well-established biomarker to diagnose acetaminophen toxicity. To date, the quantitative relationship between acetaminophen exposure, which drives adduct formation, and adduct exposure remains to be established. Our study characterized the adduct formation and disposition in adults using the approach of population parent-metabolite modeling.
View Article and Find Full Text PDFEarly acetaminophen-protein adducts predict hepatotoxicity following overdose (ATOM-5).
J Hepatol
March 2020
Department of Pharmacology, School of Medical Sciences, University of Sydney, Sydney, Australia; NSW Poisons Information Centre, Children's Hospital at Westmead, Westmead, Australia.
Background & Aims: Acetaminophen-protein adducts are specific biomarkers of toxic acetaminophen (paracetamol) metabolite exposure. In patients with hepatotoxicity (alanine aminotransferase [ALT] >1,000 U/L), an adduct concentration ≥1.0 nmol/ml is sensitive and specific for identifying cases secondary to acetaminophen.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!