The application of cytokeratin-18 as a biomarker for drug-induced liver injury.
Biomarker
Cytokeratin-18 (CK18)
Drug-induced liver injury (DILI)
Hepatotoxicity
In vivo
Journal
Archives of toxicology
ISSN: 1432-0738
Titre abrégé: Arch Toxicol
Pays: Germany
ID NLM: 0417615
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
21
04
2021
accepted:
15
07
2021
pubmed:
30
7
2021
medline:
9
2
2022
entrez:
29
7
2021
Statut:
ppublish
Résumé
Drug-induced liver injury (DILI) is a frequent and dangerous adverse effect faced during preclinical and clinical drug therapy. DILI is a leading cause of candidate drug attrition, withdrawal and in clinic, is the primary cause of acute liver failure. Traditional diagnostic markers for DILI include alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). Yet, these routinely used diagnostic markers have several noteworthy limitations, restricting their sensitivity, specificity and accuracy in diagnosing DILI. Consequently, new biomarkers for DILI need to be identified.A potential biomarker for DILI is cytokeratin-18 (CK18), an intermediate filament protein highly abundant in hepatocytes and cholangiocytes. Extensively researched in a variety of clinical settings, both full length and cleaved forms of CK18 can diagnose early-stage DILI and provide insight into the mechanism of hepatocellular injury compared to traditionally used diagnostic markers. However, relatively little research has been conducted on CK18 in preclinical models of DILI. In particular, CK18 and its relationship with DILI is yet to be characterised in an in vivo rat model. Such characterization of CK18 and ccCK18 responses may enable their use as translational biomarkers for hepatotoxicity and facilitate management of clinical DILI risk in drug development. The aim of this review is to discuss the application of CK18 as a biomarker for DILI. Specifically, this review will highlight the properties of CK18, summarise clinical research that utilised CK18 to diagnose DILI and examine the current challenges preventing the characterisation of CK18 in an in vivo rat model of DILI.
Identifiants
pubmed: 34322741
doi: 10.1007/s00204-021-03121-0
pii: 10.1007/s00204-021-03121-0
pmc: PMC8492595
doi:
Substances chimiques
Biomarkers
0
Keratin-18
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
3435-3448Informations de copyright
© 2021. The Author(s).
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