PUBLICATION
Butylated hydroxytoluene (BHT) induces zebrafish spinal cord defects and scoliosis by inhibiting the hedgehog pathway
- Authors
- Cheng, H., Li, Y., Liu, F., Zhu, S., Chen, L., Lu, H., Shi, X., Huang, L.
- ID
- ZDB-PUB-250808-12
- Date
- 2025
- Source
- Scientific Reports 15: 2885828858 (Journal)
- Registered Authors
- Keywords
- Body axis curvature, Butylated hydroxytoluene (BHT), Hedgehog (Hh) signaling pathway, Spinal cord
- MeSH Terms
-
- Animals
- Antioxidants/toxicity
- Butylated Hydroxytoluene*/toxicity
- Embryo, Nonmammalian/drug effects
- Hedgehog Proteins*/genetics
- Hedgehog Proteins*/metabolism
- Scoliosis*/chemically induced
- Scoliosis*/metabolism
- Scoliosis*/pathology
- Signal Transduction*/drug effects
- Spinal Cord*/abnormalities
- Spinal Cord*/drug effects
- Spinal Cord*/metabolism
- Zebrafish/embryology
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 40775025 Full text @ Sci. Rep.
Citation
Cheng, H., Li, Y., Liu, F., Zhu, S., Chen, L., Lu, H., Shi, X., Huang, L. (2025) Butylated hydroxytoluene (BHT) induces zebrafish spinal cord defects and scoliosis by inhibiting the hedgehog pathway. Scientific Reports. 15:2885828858.
Abstract
Butylated hydroxytoluene (BHT) is widely employed as an antioxidant in various industries. However, concerns persist regarding its safety and environmental impact, as its toxicological mechanisms remain poorly understood. Zebrafish embryos were exposed to BHT at 3, 5, and 7 mg/L to assess developmental toxicity. BHT exposure dose-dependently induced spinal cord malformations concomitant with reduced larval motility. Mechanistically, BHT suppressed Hedgehog signaling, evidenced by dysregulation of Shha, Gli1, and Smo. Notably, pharmacological activation of the Hh pathway by SAG rescued both structural defects and gene expression anomalies, confirming Hh inhibition as the primary toxicity mechanism. These results indicate that BHT inhibits Hh signaling, disrupting floor plate function and leading to spinal curvature.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping