# 3,3′,5,5′-Tetrabromobiphenyl (BB-80) and Its Hydroxylation Product (OH-BB-80) Mediate Immunotoxicity and Inhibit Embryonic Development in Zebrafish (Danio rerio) via the TLR4/NF-κB Signaling Pathway

## TL;DR

This study shows that BB-80 and OH-BB-80 harm zebrafish development and immunity by affecting the TLR4/NF-κB pathway.

## Contribution

The study reveals the immunotoxic and developmental effects of BB-80 and OH-BB-80 via the TLR4/NF-κB pathway in zebrafish.

## Key findings

- BB-80 and OH-BB-80 inhibited zebrafish embryonic development at 10 μg/L.
- Exposure increased oxidative stress and inflammation-related gene expression.
- Molecular docking confirmed stable binding of BB-80 and OH-BB-80 to TLR4.

## Abstract

Polybrominated biphenyls (PBBs) are metabolically transformed into monohydroxylated PBBs (OH-PBBs) in the environment and living organisms. Although OH-PBBs pose a significant health threat to organisms, little is known about the immunotoxicity of OH-PBBs. Therefore, the objectives of this study were to validate BB-80 and OH-BB-80 induced immunotoxicity and to explore the associated pathway mechanisms. Early development of zebrafish (Danio rerio) larvae was inhibited by 10 μg/L BB-80 and OH-BB-80, as indicated by negative changes in developmental indices. BB-80 and OH-BB-80 induced oxidative stress, significantly up-regulated reactive oxygen species (ROS) and reactive nitrogen species (RNS), and activated the antioxidant enzyme system at 10 μg/L. The mRNA expression levels of inflammatory cytokines and inflammatory chemokines were up-regulated, indicative of the onset of inflammation in zebrafish after BB-80 and OH-BB-80 exposure. In addition, downregulation of toll-like receptor 4 (TLR4), MyD88, and NF-κB pathway-related genes was observed, suggesting that BB-80 and OH-BB-80 target the TLR/NF-κB signaling pathway. Molecular docking data showed that BB-80 and OH-BB-80 bound stably to TLR4. Taken together, BB-80 and OH-BB-80 mediate immunotoxicity and early developmental suppression associated with the TLR4/NF-κB signaling pathway. Our results further the understanding of BB-80- and OH-BB-80-induced immunotoxicity, highlighting the need for toxicological studies to examine the toxic effects of the transformation products of PBBs.