The sulfate metabolite of 3,3′-dichlorobiphenyl (PCB-11) impairs Cyp1a activity and increases hepatic neutral lipids in zebrafish larvae (Danio rerio)

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. [Display omitted] •4-OH-PCB-11 is more acutely toxic than both the parent PCB-11 compound and the 4-PCB-11-Sulfate metabolite.•4-OH-PCB-11 and 4-PCB-11-Sulfate metabolites alone do not affect the Ahr pathway or morphological outcomes.•20 μM 4-PCB-11-Sulfate acute 4-day exposures inhibits Cyp1a activity in the presence of Ahr agonists.•0.2 μM 4-PCB-11-Sulfate chronic 15-day exposures increases hepatic neutral lipid accumulation.