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Totarol-1 Derivative Improves Neuronal Disability in Lead-Induced In Vivo Zebrafish Model
G Akash1, S Madesh2, Karthikeyan Ramamurthy2
1Department of Biotechnology, Faculty of Science and Humanities, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India.
Journal of Biochemical and Molecular Toxicology
|February 25, 2026
Summary
Lead exposure causes neurotoxicity, impairing memory and increasing anxiety. A novel Totarol-1 derivative effectively reduced lead in the brain, improved behavior, and corrected biochemical and genetic changes, offering a potential therapeutic strategy.
Area of Science:
- Environmental Science
- Neuroscience
- Toxicology
Background:
- Lead (Pb) exposure is a global environmental hazard with significant neurotoxic effects.
- Neurological disorders necessitate targeted therapeutic interventions.
- Zebrafish models offer a valuable platform for studying neurotoxicity and potential treatments.
Purpose of the Study:
- To investigate the neuroprotective potential of Totarol-1, a synthetic derivative, against lead-induced neurotoxicity in adult zebrafish.
- To evaluate the effects of Totarol-1 on lead accumulation, behavioral deficits, biochemical markers, and gene expression in the zebrafish brain.
Main Methods:
- Adult zebrafish were exposed to lead, and behavioral tests (T-tank, novel tank) were conducted.
- Lead levels in brain tissue were quantified.
- Biochemical markers (CAT, SOD, AChE, LPO) and gene expression (GPX4, CX43, TNF-α, IL-1β) were analyzed.
- Immunohistochemistry for α-synuclein was performed to assess Parkinson's disease-related changes.
Main Results:
- Lead exposure induced memory deficits, increased anxiety, and elevated lead accumulation in the brain.
- Lead exposure altered biochemical markers and dysregulated key genes involved in ferroptosis and neuroinflammation.
- Totarol-1 treatment significantly reduced brain lead levels, ameliorated behavioral impairments, and normalized biochemical and gene expression profiles.
- Totarol-1 decreased α-synuclein aggregation, suggesting a protective effect against lead-induced neurodegenerative changes.
Conclusions:
- Lead exposure causes widespread neurotoxic effects in zebrafish at multiple levels.
- Totarol-1 demonstrates significant neuroprotective properties against lead-induced neurotoxicity.
- Totarol-1 represents a promising therapeutic candidate for mitigating lead's detrimental effects on the brain.
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