PUBLICATION
The sulfate metabolite of 3,3'-dichlorobiphenyl (PCB-11) impairs Cyp1a activity and increases hepatic neutral lipids in zebrafish larvae (Danio rerio)
- Authors
- Roy, M.A., Duche, P.R., Timme-Laragy, A.R.
- ID
- ZDB-PUB-200722-6
- Date
- 2020
- Source
- Chemosphere 260: 127609 (Journal)
- Registered Authors
- Keywords
- 3,3′-dichlorobiphenyl, 4-PCB-11-Sulfate, Aryl hydrocarbon receptor (Ahr) pathway, Danio rerio, Developmental toxicity, Hepatotoxicity, Mixtures, PCB-11, Zebrafish, benzo[a]pyrene
- MeSH Terms
-
- Animals
- Benzo(a)pyrene/metabolism
- Cytochrome P-450 CYP1A1/metabolism
- Embryo, Nonmammalian/metabolism
- Larva/metabolism
- Lipids
- Liver/metabolism
- Polychlorinated Biphenyls/metabolism
- Polychlorinated Biphenyls/toxicity*
- Sulfates/metabolism
- Zebrafish/metabolism
- Zebrafish/physiology*
- PubMed
- 32693259 Full text @ Chemosphere
Citation
Roy, M.A., Duche, P.R., Timme-Laragy, A.R. (2020) The sulfate metabolite of 3,3'-dichlorobiphenyl (PCB-11) impairs Cyp1a activity and increases hepatic neutral lipids in zebrafish larvae (Danio rerio). Chemosphere. 260:127609.
Abstract
The environmental contaminant 3,3'-dichlorobiphenyl (PCB-11) is widely detected in environmental samples, and this parent compound along with its metabolites 4-OH-PCB-11 and 4-PCB-11-Sulfate are detected in human serum. Our previous research in zebrafish (Danio rerio) embryos shows exposure to 20 μM PCB-11 inhibits Cyp1a enzyme activity and perturbs lipid metabolism pathways. In this study, wildtype AB embryos underwent acute exposures from 1 to 4 days post fertilization (dpf) to 0.002-20 μM 4-OH-PCB-11 or 0.2-20 μM 4-PCB-11-Sulfate, with and without co-exposures to 100 μg/L benzo[a]pyrene (B[a]P) or 5 nM 3,3',4,4',5-pentachlorobiphenyl (PCB-126), and were assessed for in vivo EROD activity and morphometrics. Chronic exposures from 1 to 15 dpf to assess lipid accumulation using Oil-Red-O staining were also conducted with 0.2 μM parent or metabolite compounds, alongside a co-exposure experiment of 0.002-0.2 μM 4-PCB-11-Sulfate and 10 μg/L B[a]P. For acute experiments, 2 and 20 μM 4-OH-PCB-11 was lethal but no Cyp1a or morphological effects were observed at lower concentrations; 20 μM 4-PCB-11-Sulfate significantly lowered the Cyp1a activity of B[a]P and PCB-126 but did not alter morphological development. For chronic experiments, 0.2 μM 4-PCB-11-Sulfate significantly increased lipid accumulation 30% in single exposures and 44% in co-exposures with B[a]P. Further long-term studies would better elucidate the effects of this contaminant, particularly in the context of environmentally-relevant mixtures.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping