Compromised blood-bile barrier after acetaminophen overdose.
Arch Toxicol
; 96(10): 2825-2827, 2022 10.
Article
en En
| MEDLINE
| ID: mdl-35849165
ABSTRACT
N-acetylcysteine (NAC) is the only approved drug for the treatment of acetaminophen (APAP) intoxication. A limitation of NAC is the short therapeutic time-window as it is only effective within approximately eight hours after APAP ingestion, which is critical since patients seek medical attention often after the onset of symptoms approximately 24 h after overdose. Recently, a so far unknown mechanism was identified by which APAP causes an increase of intracellular bile acid concentrations in hepatocytes to concentrations that exceed cytotoxic thresholds. APAP compromises the tight junctions of bile canaliculi that leads to the leakage of highly concentrated bile acids into the sinusoids. From the sinusoidal blood, a high fraction of the released bile acids is transported back into hepatocytes by basolateral uptake carriers and secreted into bile canaliculi. Repeated leakage from the canaliculi followed by hepatocellular reuptake and canalicular secretion causes an increase of intracellular bile acid concentrations and finally hepatocyte death. Importantly, inhibition of bile acid uptake carriers reduced intracellular bile acid concentrations and strongly ameliorated APAP hepatotoxicity, a finding that could result in a new therapeutic option for APAP-intoxicated patients.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedad Hepática Inducida por Sustancias y Drogas
/
Sobredosis de Droga
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Arch Toxicol
Año:
2022
Tipo del documento:
Article
País de afiliación:
Egipto