Morin attenuates trimethyltin-induced hippocampal neurotoxicity in male rats by mitigating oxidative stress, inflammation, and apoptosis

Morin (3,5,7,2',4'-pentahydroxyflavone) is a natural flavonoid with potent antioxidant, anti-inflammatory, and neuroprotective properties. Trimethyltin (TMT) is a selective neurotoxin inducing hippocampal degeneration and cognitive deficits. This study investigated morin's protective effects against TMT-induced neurotoxicity. Male Wistar rats received a single TMT injection (8 mg/kg, i.p.), followed by oral morin (25, 50, 100 mg/kg) for 10 days. Cognitive and anxiety-like behaviors were assessed via Open Field, Y-maze, Radial Arm Maze (RAM), and Elevated Plus Maze (EPM) tests. Systemic oxidative stress, hippocampal malondialdehyde (MDA), interleukin (IL)-6, and tumor necrosis factor-alpha (TNF-α) were quantified. Histological changes in CA1/CA3 subfields were evaluated using H&E and NeuN/cleaved caspase-3 double immunofluorescence. TMT impaired memory, increased anxiety, and induced oxidative stress, inflammation, and apoptosis. While morin did not alter TMT-induced hyperlocomotion in the open field, the 50 mg/kg dose effectively normalized exploratory activity and significantly attenuated spatial memory impairments in Y-maze and RAM (50 mg/kg). Morin also reduced anxiety-like behavior and suppressed oxidative stress and pro-inflammatory cytokine concentrations. Furthermore, morin preserved neuronal density, reduced non-neuronal hypercellularity, and decreased the apoptotic index in CA1/CA3 subfields. In conclusion, morin exerts robust neuroprotective effects by mitigating inflammation and apoptosis, providing novel evidence for its therapeutic potential against TMT-induced neurodegeneration, with 50 mg/kg identified as the most consistently effective dose.