Role of vitamin D3 in mitigating sodium arsenite-induced neurotoxicity in male rats

Arsenic is associated with various neurological disorders, notably affecting memory and cognitive functions. The current study examined the protective effects of vitamin D₃ (Vit. D₃) in countering oxidative stress, neuroinflammation and apoptosis induced by sodium arsenite (SA) in the cerebral cortex of rats. Male Wistar rats were subjected to a daily oral administration of sodium arsenite (NaAsO₂, SA) at a dosage of 5 mg/kg, along with 500 IU/kg of Vit. D₃, and a combination of both substances for four weeks. The results indicated that Vit. D₃ effectively mitigated the SA-induced increase in oxidative stress markers, thiobarbituric acid reactive substances (TBARS) and nitric oxide (NO), the decrease in antioxidants (reduced glutathione; GSH, superoxide dismutase; SOD, catalase; CAT, and glutathione peroxidase; GPx), as well as the increase in pro-inflammatory markers including, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and amyloid-beta (Aβ)1-42. Furthermore, Vit. D₃ reversed the alterations in the neurochemicals acetylcholinesterase (AchE), monoamine oxidase (MAO), dopamine (DA), and acetylcholine (Ach) and ameliorated the histopathological changes in the cerebral cortex. Moreover, immunohistochemical analyses revealed that Vit. D₃ reduced the SA-induced overexpression of cerebral cysteine aspartate-specific protease-3 (caspase-3) and glial fibrillary acidic protein (GFAP) in the cerebral cortex of male rats. Consequently, the co-administration of Vit. D₃ can protect the cerebral cortex against SA-induced neurotoxicity, primarily through its antioxidant, anti-inflammatory, anti-apoptotic, and anti-astrogliosis effects.