Akash_2026_J.Biochem.Mol.Toxicol_40_e70762

A worldwide environmental danger resulting from extensive pollution, lead (Pb) exposure has significant neurotoxic potential. Neurological disorders underscore the necessity for effective therapeutic approaches modified to particular conditions. To evaluate the potential advantages of brain neuroplasticity, this work tests Totarol-1, a new synthetic derivative, in the adult zebrafish model. Lead causes notable behavioral impairments, including memory loss, as evaluated by the T-tank test, and increased anxiety reactions, measured by the novel tank test, along with noticeably greater lead buildup in brain tissue. Moreover, lead exposure may alter biochemical tests, including catalase (CAT), superoxide dismutase (SOD), acetylcholinesterase (AChE), and lipid peroxidase (LPO). Key genes related to ferroptosis and neuroinflammation, including GPX4, CX43, TNF-alpha, and IL-1beta, were identified as dysregulated through molecular gene analysis, in which GPX4A and CX43 showing marked changes, indicating either reduced levels of ferroptosis or restoration of neuronal gap junctions. Treatment with the Totarol-1 derivative notably reduced lead accretion in the brain and altered behavioral impairments, biochemical markers, and gene expression. Furthermore, the immunochemistry of the brain was examined using an alpha-synuclein protein in Parkinson's disease (PD). The clump of this protein in the lead exposure group indicated a neurological condition, and was decreased due to Totarol-1 derivative therapy techniques against lead-induced neurotoxicity models. This work reveals that lead treatment in the zebrafish brain causes deficits at various organisational levels, which were corrected by Totarol-1 derivative, thereby improving brain neuronal disability.