Association of novel markers of liver disease with neonatal liver disease in premature baboons, Papio sp.
Animals
Animals, Newborn
Biomarkers
/ blood
Disease Models, Animal
Female
Hyaluronic Acid
/ blood
Kupffer Cells
/ pathology
Liver Diseases
/ etiology
Male
Papio
Parenteral Nutrition
/ adverse effects
Premature Birth
Primate Diseases
/ chemically induced
Tissue Inhibitor of Metalloproteinase-1
/ blood
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
26
06
2019
accepted:
09
01
2020
entrez:
10
3
2020
pubmed:
10
3
2020
medline:
13
6
2020
Statut:
epublish
Résumé
Parenteral Nutrition (PN) Associated Liver Disease (PNALD) affects up to 60% of neonates; however, techniques for diagnosing and monitoring disease progression remain limited. The neonatal baboon model may provide a unique opportunity to identify serologic markers associated with this disease. The purpose of this study was to investigate if Hyaluronic Acid (HA), TIMP metallopeptidase inhibitor 1 (TIMP1), Amino-terminal Propeptide of Type-III Collagen (PIIINP) and Enhanced Liver Fibrosis (ELF) score associate with histological liver disease in neonatal baboons exposed to PN. Preterm baboons delivered via c-section at 67% gestation received PN for 14 days with or without Intralipid (PRT+IL, PRT-IL, respectively) or were sacrificed after birth (PRTCTR). Term baboons were sacrificed after birth (TERMCTR) or survived 14 days (TERM+14d). Serum HA, TIMP1, and PIIINP concentrations were measured by ELISA. A blinded pathologist assigned liver histological scores following necropsy. HA increased 9.1-fold, TIMP1 increased 2.2-fold, and ELF score increased 1.4-fold in PRT-IL compared to PRTCTR. ALT, AST, and GGT were within normal limits and did not vary between groups. A trend towards increased fibrosis was found in PRT-IL baboons. Microvesicular hepatocyte steatosis and Kupffer cell hypertrophy were elevated in PRT-IL vs PRTCTR. HA and TIMP1 were significantly elevated in preterm baboons with early histological findings of liver disease evidenced by hepatic steatosis, Kupffer cell hypertrophy and a trend towards fibrosis whereas traditional markers of liver disease remained normal. These novel markers could potentially be utilized for monitoring early hepatic injury in neonates.
Identifiants
pubmed: 32150543
doi: 10.1371/journal.pone.0228985
pii: PONE-D-19-18073
pmc: PMC7062281
doi:
Substances chimiques
Biomarkers
0
Tissue Inhibitor of Metalloproteinase-1
0
Hyaluronic Acid
9004-61-9
Banques de données
figshare
['10.6084/m9.figshare.8326532']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0228985Subventions
Organisme : NIH HHS
ID : P51 OD011133
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR025767
Pays : United States
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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