Protective role of Karanjin against bisphenol A-Induced cognitive deficits and oxidative damage in a zebrafish model

Bisphenol A (BPA), a persistent environmental contaminant with endocrine-disrupting properties, has been extensively linked to neurotoxicity, leading to cognitive decline, synaptic dysfunction, and neuronal degeneration. It crosses the blood-brain barrier and induces oxidative stress, mitochondrial impairment, and neuroinflammation, leading to neurodegenerative diseases such as Alzheimer's disease. This study investigates the neuroprotective effects of karanjin, a naturally occurring furanoflavonoid, against BPA-induced neurotoxicity using zebrafish (Danio rerio) as a model organism. Adult zebrafish were exposed to 4 mg/L BPA for 21 days, followed by karanjin supplementation at 5 mg/L and 10 mg/L. Standard neuroprotective agents, donepezil and mentat, were used for comparison. Behavioral assessments, including novel tank diving, T-maze, novel object recognition, and Y-maze tests, showed that BPA exposure caused significant impairments in exploratory behavior, learning, and memory, which were reversed by high-dose karanjin. Biochemical analysis indicated BPA exposure elevated acetylcholinesterase (AChE) activity, which was significantly reduced by karanjin. Furthermore, karanjin restored glutathione (GSH) levels, increased superoxide dismutase (SOD) activity, and reduced lipid peroxidation (LPO), indicating strong antioxidant capacity. Histopathological evaluation confirmed karanjin's neuroprotective effects by preserving neuronal integrity and preventing degeneration. These findings suggest karanjin exhibits neuroprotective potential comparable to FDA-approved drugs, warranting further research for therapeutic applications in neurodegenerative disorders.