Environmental perfluoroalkyl acid exposures are associated with liver disease characterized by apoptosis and altered serum adipocytokines.
Cytokeratin 18
Non-alcoholic fatty liver disease (NAFLD)
Perfluoroalkyl acids (PFAAs)
Perfluorooctanoic acid (PFOA)
Tumor necrosis factor alpha (TNFα)
Journal
Environmental pollution (Barking, Essex : 1987)
ISSN: 1873-6424
Titre abrégé: Environ Pollut
Pays: England
ID NLM: 8804476
Informations de publication
Date de publication:
Apr 2019
Apr 2019
Historique:
received:
13
09
2018
revised:
13
01
2019
accepted:
16
01
2019
entrez:
3
3
2019
pubmed:
3
3
2019
medline:
23
4
2019
Statut:
ppublish
Résumé
Exposures to perfluoroalkyl substances (PFAS) including perfluoroalkyl acids (PFAAs) are associated with increased liver enzymes in cohort studies including the C8 Health Study. In animal models, PFAAs disrupt hepatic lipid metabolism and induce apoptosis to cause nonalcoholic fatty liver disease (NAFLD). PFAAs are immunotoxic and inhibit pro-inflammatory cytokine release from stimulated leukocytes in vitro. This cross-sectional study tests the hypothesis that environmental PFAAs are associated with increased hepatocyte apoptosis and decreased pro-inflammatory cytokines in serum. Biomarkers previously associated with PFAS exposures and/or NAFLD were evaluated as secondary endpoints. Two hundred adult C8 Health Study participants were included. Measured serum biomarkers included: perfluorohexane sulfonate (PFHxS); perfluorooctanoic acid (PFOA); perfluorooctane sulfonate (PFOS); perfluorononanoic acid (PFNA); cytokeratin 18 M30 (CK18 M30, hepatocyte apoptosis); adipocytokines; insulin; and cleaved complement 3 (C3a). Confounder-adjusted linear regression models determined associations between PFAS and disease biomarkers with cut-offs determined by classification and regression tree analysis. CK18 M30 was positively associated with PFHxS (β = 0.889, p = 0.042); PFOA (β = 2.1, p = 0.005); and PFNA (β = 0.567, p = 0.03). Tumor necrosis factor α (TNFα) was inversely associated with PFHxS (β = -0.799, p = 0.001); PFOA (β = - 1.242, p = 0.001); and PFOS (β = -0.704, p < 0.001). Interleukin 8 was inversely associated with PFOS and PFNA. PFAAs were also associated with sexually dimorphic adipocytokine and C3a responses. Overall, PFAA exposures were associated with the novel combination of increased biomarkers of hepatocyte apoptosis and decreased serum TNFα. These data support previous findings from cohorts and experimental systems that PFAAs may cause liver injury while downregulated some aspects of the immune response. Further studies of PFAAs in NAFLD are warranted and should evaluate sex differences.
Identifiants
pubmed: 30823334
pii: S0269-7491(18)34159-9
doi: 10.1016/j.envpol.2019.01.064
pmc: PMC6404528
mid: NIHMS1521335
pii:
doi:
Substances chimiques
Adipokines
0
Biomarkers
0
Fluorocarbons
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1055-1063Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM113226
Pays : United States
Organisme : NIAAA NIH HHS
ID : P50 AA024337
Pays : United States
Organisme : NIEHS NIH HHS
ID : R35 ES028373
Pays : United States
Organisme : NIEHS NIH HHS
ID : P42 ES023716
Pays : United States
Organisme : NIEHS NIH HHS
ID : T32 ES011564
Pays : United States
Organisme : NIGMS NIH HHS
ID : U54 GM104942
Pays : United States
Informations de copyright
Published by Elsevier Ltd.
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