PUBLICATION
Probing the hepatotoxicity mechanisms of novel chlorinated polyfluoroalkyl sulfonates to zebrafish larvae: Implication of structural specificity
- Authors
- Yi, S., Chen, P., Yang, L., Zhu, L.
- ID
- ZDB-PUB-191031-14
- Date
- 2019
- Source
- Environment International 133: 105262 (Journal)
- Registered Authors
- Keywords
- Hepatic steatosis, Novel chlorinated polyfluoroalkyl alternatives, Structure-dependent mode-of-action, Zebrafish larvae
- MeSH Terms
-
- Alkanesulfonic Acids/chemistry
- Alkanesulfonic Acids/toxicity*
- Animals
- Fluorocarbons/chemistry
- Fluorocarbons/toxicity*
- Larva/drug effects
- Liver/drug effects*
- Molecular Docking Simulation
- Structure-Activity Relationship
- Water Pollutants, Chemical/chemistry
- Water Pollutants, Chemical/toxicity*
- Zebrafish/metabolism*
- PubMed
- 31665679 Full text @ Environ. Int.
Citation
Yi, S., Chen, P., Yang, L., Zhu, L. (2019) Probing the hepatotoxicity mechanisms of novel chlorinated polyfluoroalkyl sulfonates to zebrafish larvae: Implication of structural specificity. Environment International. 133:105262.
Abstract
Hepatotoxicity in zebrafish (Danio rerio) larvae elicited by legacy perfluorooctane sulfonate (PFOS) and its three novel chlorinated alternatives, including chlorinated polyfluorooctane sulfonate (Cl-PFOS) and chlorinated polyfluoroalkyl ether sulfonates (6:2 and 8:2 Cl-PFESA analogs), was evaluated in this study. Upon 7-day separate exposure to the four target compounds at 1 µmol/L, significant hepatic steatosis in exposed larvae was evidenced by pathological micro/macro vacuolation, which was presumably attributed to the excess accumulation of lipid, especially the overloaded triglyceride (TG) level. Disruption on gene transcription was subjected to a structure-dependent manner. In general, PFOS, Cl-PFOS and 6:2 Cl-PFESA of the identical carbon chain length (i.e. C8), despite with different substituents, displayed a similar activation mode and comparable disruptive potency on lipid metabolism responsive genes, which particularly promoted fatty acid synthesis (acetyl-CoA carboxylase, acacb) and β-oxidation (cytochrome P450 enzymes-1A, cyp1a; peroxisomal acyl-CoA oxidase 1, acox1; and acyl-CoA dehy-drogenase, acadm). However, 8:2 Cl-PFESA with a prolonged carbon chain length (i.e. C10), preferentially disturbed fatty acid exportation (apolipoprotein-B100, apob) and triggered a different modulation pattern on fatty acid β-oxidation against the other three compounds. Molecular docking analysis indicated that 8:2 Cl-PFESA exhibited considerably higher peroxisome proliferator-activated receptors (PPARs) antagonism than others, corresponding to its unique suppression effect on fatty acid β-oxidation responsive genes. To our knowledge, this is the first in vivo study reporting hepatotoxicity of Cl-PFOS and Cl-PFESAs to aquatic organisms. Although characterized with different toxic mode-of-action, these novel alternatives can elicit hepatic steatosis as strong as PFOS, stressing the biological risks in view of their global contamination.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping