N-Acetyl cysteine does not prevent liver toxicity from chronic low-dose plus subacute high-dose paracetamol exposure in young or old mice

Fundamental & Clinical Pharmacology
Alice-Elizabeth KaneSarah-Nicole Hilmer

Abstract

Paracetamol is an analgesic commonly used by people of all ages, which is well documented to cause severe hepatotoxicity with acute overexposures. The risk of hepatotoxicity from nonacute paracetamol exposures is less extensively studied, and this is the exposure most common in older adults. Evidence on the effectiveness of N-acetyl cysteine (NAC) for nonacute paracetamol exposures, in any age group, is lacking. This study aimed to examine the effect of long-term exposure to therapeutic doses of paracetamol and subacute paracetamol overexposure, in young and old mice, and to investigate whether NAC was effective at preventing paracetamol hepatotoxicity induced by these exposures. Young and old male C57BL/6 mice were fed a paracetamol-containing (1.33 g/kg food) or control diet for 6 weeks. Mice were then dosed orally eight times over 3 days with additional paracetamol (250 mg/kg) or saline, followed by either one or two doses of oral NAC (1200 mg/kg) or saline. Chronic low-dose paracetamol exposure did not cause hepatotoxicity in young or old mice, measured by serum alanine aminotransferase (ALT) elevation, and confirmed by histology and a DNA fragmentation assay. Subacute paracetamol exposure caused significant hepatotoxicity ...Continue Reading

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Citations

Feb 28, 2020·Science Translational Medicine·Alessandro MagrìAlberto Bardelli
Nov 21, 2019·Mini Reviews in Medicinal Chemistry·Annalise R PfaffNuran Ercal
Aug 13, 2017·Fundamental & Clinical Pharmacology·Sael Casas-GrajalesPablo Muriel
Jul 18, 2021·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Karin HedenmalmRob Flynn

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