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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift


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.


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Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Farmakologi och toxikologi
Sidor (från-till)589-593
TidskriftBasic and Clinical Pharmacology and Toxicology
Utgåva nummer5
Tidigt onlinedatum2018 jun 16
StatusPublished - 2018
Peer review utfördJa

Relaterad forskningsoutput

Johan Nilsson, 2018, Lund: Lund University: Faculty of Medicine. 58 s.

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

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