3,3′,5,5′-Tetrabromobiphenyl (BB-80) and Its Hydroxylation Product (OH-BB-80) Mediate Immunotoxicity and Inhibit Embryonic Development in Zebrafish (<i>Danio rerio</i>) via the TLR4/NF-κB Signaling Pathway
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 wer...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-04-01
|
| Series: | Toxics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2305-6304/13/4/293 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849714261723447296 |
|---|---|
| author | Yongjian Shao Yinan Zhang Xiaofang Zhang Yu Han Zhiquan Liu Jiafeng Ding Binhao Wang Hangjun Zhang |
| author_facet | Yongjian Shao Yinan Zhang Xiaofang Zhang Yu Han Zhiquan Liu Jiafeng Ding Binhao Wang Hangjun Zhang |
| author_sort | Yongjian Shao |
| collection | DOAJ |
| description | 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 (<i>Danio rerio</i>) 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. |
| format | Article |
| id | doaj-art-a2cc02c1fe5f47b2a15e09a853f22a39 |
| institution | DOAJ |
| issn | 2305-6304 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxics |
| spelling | doaj-art-a2cc02c1fe5f47b2a15e09a853f22a392025-08-20T03:13:45ZengMDPI AGToxics2305-63042025-04-0113429310.3390/toxics130402933,3′,5,5′-Tetrabromobiphenyl (BB-80) and Its Hydroxylation Product (OH-BB-80) Mediate Immunotoxicity and Inhibit Embryonic Development in Zebrafish (<i>Danio rerio</i>) via the TLR4/NF-κB Signaling PathwayYongjian Shao0Yinan Zhang1Xiaofang Zhang2Yu Han3Zhiquan Liu4Jiafeng Ding5Binhao Wang6Hangjun Zhang7College of Engineering, Hangzhou Normal University, Hangzhou 311121, ChinaCollege of Engineering, Hangzhou Normal University, Hangzhou 311121, ChinaCollege of Engineering, Hangzhou Normal University, Hangzhou 311121, ChinaCollege of Engineering, Hangzhou Normal University, Hangzhou 311121, ChinaCollege of Engineering, Hangzhou Normal University, Hangzhou 311121, ChinaCollege of Engineering, Hangzhou Normal University, Hangzhou 311121, ChinaCollege of Engineering, Hangzhou Normal University, Hangzhou 311121, ChinaCollege of Engineering, Hangzhou Normal University, Hangzhou 311121, ChinaPolybrominated 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 (<i>Danio rerio</i>) 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.https://www.mdpi.com/2305-6304/13/4/293immunotoxicityinflammationoxidative stressTLR4/NF-κBzebrafish |
| spellingShingle | Yongjian Shao Yinan Zhang Xiaofang Zhang Yu Han Zhiquan Liu Jiafeng Ding Binhao Wang Hangjun Zhang 3,3′,5,5′-Tetrabromobiphenyl (BB-80) and Its Hydroxylation Product (OH-BB-80) Mediate Immunotoxicity and Inhibit Embryonic Development in Zebrafish (<i>Danio rerio</i>) via the TLR4/NF-κB Signaling Pathway Toxics immunotoxicity inflammation oxidative stress TLR4/NF-κB zebrafish |
| title | 3,3′,5,5′-Tetrabromobiphenyl (BB-80) and Its Hydroxylation Product (OH-BB-80) Mediate Immunotoxicity and Inhibit Embryonic Development in Zebrafish (<i>Danio rerio</i>) via the TLR4/NF-κB Signaling Pathway |
| title_full | 3,3′,5,5′-Tetrabromobiphenyl (BB-80) and Its Hydroxylation Product (OH-BB-80) Mediate Immunotoxicity and Inhibit Embryonic Development in Zebrafish (<i>Danio rerio</i>) via the TLR4/NF-κB Signaling Pathway |
| title_fullStr | 3,3′,5,5′-Tetrabromobiphenyl (BB-80) and Its Hydroxylation Product (OH-BB-80) Mediate Immunotoxicity and Inhibit Embryonic Development in Zebrafish (<i>Danio rerio</i>) via the TLR4/NF-κB Signaling Pathway |
| title_full_unstemmed | 3,3′,5,5′-Tetrabromobiphenyl (BB-80) and Its Hydroxylation Product (OH-BB-80) Mediate Immunotoxicity and Inhibit Embryonic Development in Zebrafish (<i>Danio rerio</i>) via the TLR4/NF-κB Signaling Pathway |
| title_short | 3,3′,5,5′-Tetrabromobiphenyl (BB-80) and Its Hydroxylation Product (OH-BB-80) Mediate Immunotoxicity and Inhibit Embryonic Development in Zebrafish (<i>Danio rerio</i>) via the TLR4/NF-κB Signaling Pathway |
| title_sort | 3 3 5 5 tetrabromobiphenyl bb 80 and its hydroxylation product oh bb 80 mediate immunotoxicity and inhibit embryonic development in zebrafish i danio rerio i via the tlr4 nf κb signaling pathway |
| topic | immunotoxicity inflammation oxidative stress TLR4/NF-κB zebrafish |
| url | https://www.mdpi.com/2305-6304/13/4/293 |
| work_keys_str_mv | AT yongjianshao 3355tetrabromobiphenylbb80anditshydroxylationproductohbb80mediateimmunotoxicityandinhibitembryonicdevelopmentinzebrafishidaniorerioiviathetlr4nfkbsignalingpathway AT yinanzhang 3355tetrabromobiphenylbb80anditshydroxylationproductohbb80mediateimmunotoxicityandinhibitembryonicdevelopmentinzebrafishidaniorerioiviathetlr4nfkbsignalingpathway AT xiaofangzhang 3355tetrabromobiphenylbb80anditshydroxylationproductohbb80mediateimmunotoxicityandinhibitembryonicdevelopmentinzebrafishidaniorerioiviathetlr4nfkbsignalingpathway AT yuhan 3355tetrabromobiphenylbb80anditshydroxylationproductohbb80mediateimmunotoxicityandinhibitembryonicdevelopmentinzebrafishidaniorerioiviathetlr4nfkbsignalingpathway AT zhiquanliu 3355tetrabromobiphenylbb80anditshydroxylationproductohbb80mediateimmunotoxicityandinhibitembryonicdevelopmentinzebrafishidaniorerioiviathetlr4nfkbsignalingpathway AT jiafengding 3355tetrabromobiphenylbb80anditshydroxylationproductohbb80mediateimmunotoxicityandinhibitembryonicdevelopmentinzebrafishidaniorerioiviathetlr4nfkbsignalingpathway AT binhaowang 3355tetrabromobiphenylbb80anditshydroxylationproductohbb80mediateimmunotoxicityandinhibitembryonicdevelopmentinzebrafishidaniorerioiviathetlr4nfkbsignalingpathway AT hangjunzhang 3355tetrabromobiphenylbb80anditshydroxylationproductohbb80mediateimmunotoxicityandinhibitembryonicdevelopmentinzebrafishidaniorerioiviathetlr4nfkbsignalingpathway |