N,N'-Bis(2-mercaptoethyl)isophthalamide Binds Electrophilic Paracetamol Metabolites and Prevents Paracetamol-Induced Liver Toxicity

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Bibtex

@article{133c0b8a832f4c2abed310ea29d9cac1,
title = "N,N'-Bis(2-mercaptoethyl)isophthalamide Binds Electrophilic Paracetamol Metabolites and Prevents Paracetamol-Induced Liver Toxicity",
abstract = "Paracetamol overdosing may cause liver injury including fulminant liver failure due to generation of the toxic metabolites, N-acetyl-p-benzoquinone imine (NAPQI) and p-benzoquinone (p-BQ). Herein, the chelating agent, N,N'-Bis(2-mercaptoethyl)isophthalamide (NBMI), was examined for its potential ability to entrap NAPQI and p-BQ and to prevent paracetamol-induced liver injury. Both NBMI and the conventional paracetamol antidote N-acetylcysteine (NAC) were investigated with regard to their abilities to scavenge the NAPQI and p-BQ in a Transient Receptor Potential Ankyrin 1-dependent screening assay. Stoichiometric evaluations indicated that NBMI was able to entrap these metabolites more efficiently than NAC. Furthermore, oral administration of either NBMI (680 mg/kg) or NAC (680 mg/kg) prevented the development of the characteristic liver necrosis and elevation of serum alanine aminotransferase in a mouse model for paracetamol-induced liver injury. In summary, these results show that NBMI is able to entrap the toxic metabolites NAPQI and p-BQ and to prevent paracetamol-induced liver injury in mice.",
author = "Nilsson, {Johan L.{\AA}.} and Anders Blomgren and Nilsson, {Ulf J.} and H{\"o}gest{\"a}tt, {Edward D.} and Lars Grundemar",
year = "2018",
doi = "10.1111/bcpt.13058",
language = "English",
volume = "123",
pages = "589--593",
journal = "Basic and Clinical Pharmacology and Toxicology",
issn = "1742-7843",
publisher = "Wiley-Blackwell",
number = "5",

}