PUBLICATION
Butylated Hydroxyanisole (BHA) Disrupts Brain Signalling in Embryo-Larval Stage of Zebrafish Leading to Attention Deficit Hyperactivity Disorder (ADHD)
- Authors
- Veshaal, K., Vasantharekha, R., Balu, U.R., Aayush, M.V., Pillai, S.S.B., Santosh, W., Seetharaman, B.
- ID
- ZDB-PUB-250724-19
- Date
- 2025
- Source
- Journal of xenobiotics 15: (Journal)
- Registered Authors
- Keywords
- ADHD, butylated hydroxyanisole, developmental toxicity, neurotoxicity, zebrafish embryo
- MeSH Terms
- none
- PubMed
- 40700163 Full text @ J Xenobiot
Citation
Veshaal, K., Vasantharekha, R., Balu, U.R., Aayush, M.V., Pillai, S.S.B., Santosh, W., Seetharaman, B. (2025) Butylated Hydroxyanisole (BHA) Disrupts Brain Signalling in Embryo-Larval Stage of Zebrafish Leading to Attention Deficit Hyperactivity Disorder (ADHD). Journal of xenobiotics. 15:.
Abstract
Background Butylated hydroxyanisole (BHA) has been extensively used in several commercial industries as a preservative. It causes severe cellular and neurological damage affecting the developing fetus and might induce attention deficit hyperactivity disorder (ADHD).
Methods Zebrafish embryos were subjected to five distinct doses of BHA-0.5, 1, 2, 4, and 8 ppb up to 96 h post fertilization (hpf). Hatching rate, heart rate, and body malformations were assessed at 48 hpf, 72 hpf, and 48-96 hpf, respectively. After exposure, apoptotic activity, neurobehavioral evaluation, neurotransmitter assay, and antioxidant activity were assessed at 96 hpf. At 120 hpf, the expression of genes DRD4, COMT, 5-HTR1aa, and BDNF was evaluated by real-time PCR.
Results BHA exposure showed a delay in the hatching rate and a decrease in the heart rate of the embryo when compared with the control. Larvae exhibited developmental deformities such as bent spine, yolk sac, and pericardial edema. A higher density of apoptotic cells was observed in BHA-exposed larvae at 96 hpf. There was a decline in catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and superoxide dismutase (SOD) activity, indicating oxidative stress. There was a significant decrease in Acetylcholinesterase (AChE) activity and serotonin levels with an increase in concentration of BHA, leading to a dose-responsive increase in anxiety and impairment in memory. A significant decrease in gene expression was also observed for DRD4, COMT, 5-HTR1aa, and BDNF.
Conclusions Even at lower concentrations of BHA, zebrafish embryos suffered from developmental toxicity, anxiety, and impaired memory due to a decrease in AChE activity and serotonin levels and altered the expression of the mentioned genes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping