Liver Regeneration after Acetaminophen Hepatotoxicity: Mechanisms and Therapeutic Opportunities.
Journal
The American journal of pathology
ISSN: 1525-2191
Titre abrégé: Am J Pathol
Pays: United States
ID NLM: 0370502
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
28
09
2018
revised:
11
12
2018
accepted:
17
12
2018
pubmed:
18
1
2019
medline:
28
12
2019
entrez:
18
1
2019
Statut:
ppublish
Résumé
Acetaminophen (N-acetyl-para-aminophenol; APAP) overdose is the most common cause of acute liver failure in the Western world, with limited treatment opportunities. For years, research on APAP overdose has been focused on investigating the mechanisms of hepatotoxicity, with limited success in advancing therapeutic strategies. Acute liver injury after any insult, including APAP overdose, is followed by compensatory liver regeneration, which promotes recovery and is a crucial determinant of the final outcome. Liver regeneration after APAP-induced liver injury is dose dependent and impaired after severe APAP overdose. Although robust regenerative response is associated with spontaneous recovery and survival, impaired regeneration results in faster progression of injury and death after APAP overdose. APAP hepatotoxicity-induced liver regeneration involves a complex time- and dose-dependent interplay of several signaling mediators, including growth factors, cytokines, angiogenic factors, and other mitogenic pathways. Compared with the liver injury, which is established before most patients seek medical attention and has proved difficult to manipulate, liver regeneration can be potentially modulated even in late-stage APAP-induced acute liver failure. Despite recent efforts to study the mechanisms of liver regeneration after APAP-induced liver injury, more comprehensive research in this area is required, especially regarding factors that contribute to impaired regenerative response, to develop novel regenerative therapies for APAP-induced acute liver failure.
Identifiants
pubmed: 30653954
pii: S0002-9440(18)30845-9
doi: 10.1016/j.ajpath.2018.12.006
pmc: PMC6446224
pii:
doi:
Substances chimiques
Analgesics, Non-Narcotic
0
Acetaminophen
362O9ITL9D
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
719-729Subventions
Organisme : NIGMS NIH HHS
ID : P30 GM118247
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK098414
Pays : United States
Informations de copyright
Copyright © 2019 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
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