El Dien_2026_Tissue.Cell_101_103459

This research investigated the potential of alpha-lipoic acid (ALA) to mitigate neurotoxicity caused by multi-walled carbon nanotubes (MWCNTs). Forty albino rats were allocated into four groups. The control group was given 1% Tween-80 for five days. ALA group (received ALA at a dose of 200 mg/kg for ten days), MWCNTs group (given MWCNTs at a concentration of 0.5 mg/kg for 5 days), and MWCNTs + ALA group (administered MWCNTs at 0.5 mg/kg for a duration of five days, then ALA at 200 mg/kg for ten days). Behavioral assessments were conducted 24 h following the final administration, and then the rats were subjected to euthanasia. Brain samples were acquired for biochemical, molecular, histological, and immunohistochemical examinations. This study revealed that the administration of MWCNTs induced neurobehavioral alterations and neurotoxicity in rats, as indicated by inflammation, increased oxidative stress, and apoptosis in the brain. Biochemically, MWCNTs markedly declined acetylcholinesterase (AChE) gene expression (0.45, 0.52, and 0.45-fold in the cerebral cortex, cerebellar cortex, and hippocampus, respectively) (P < 0.05). Histopathological examination revealed degenerative changes of neurons in the cerebral cortex, hippocampus, and cerebellum. Immunohistochemical evaluation demonstrated a significant increase in cyclooxygenase-2 (COX-2), caspase-3, and glial fibrillary acidic protein (GFAP) immunoreactivity (P < 0.05). Concurrently, ALA therapy mitigated the neurotoxicity produced by MWCNTs. In conclusion, ALA may mitigate neurotoxicity generated by MWCNTs via anti-inflammatory, antioxidant, and anti-apoptotic pathways.