Neurobehavioral and Neuropathological Alterations Induced by Nickel Sulphate Toxicity in Rats: Molecular Mechanisms and Prophylaxis with Curcumin Supplementation

Nickel is recognized as an environmental contaminant and can affect various living organisms; therefore, clarifying the mechanism of Ni-induced toxicity and elucidating a protection strategy are crucial. This study investigated the neurotoxic potential of dosing nickel sulfate (Ni) on rats and the possible protective mechanism of curcumin in alleviating brain injury. Twenty-eight male albino Wistar rats were allocated into four groups: G1; control, G2; curcumin (CUR, 1.5 mg/kg bwt/day, i.p), G3; nickel sulfate (Ni, 20 mg/kg bwt, per os), and G4; Ni + CUR by the same protocol dosing for 30 days. Results revealed that Ni induced neurobehavioral abnormalities including disruption in cognition, impaired memory, increased anxiety, and motor imbalance, impaired acetylcholinesterase expression, and disrupted brain redox state. Downregulation of Nrf2 and HO-1 expression was recorded; moreover, marked neuropathological alterations affect many brain areas, mainly the cerebrum, hippocampus, and cerebellum, with increased immune reactivity of caspase-3 and NF-κB. However, curcumin significantly reduces brain injury via down-regulation of the redox state and regresses the related neurobehavioral and neuropathological alterations. The role of curcumin in the mitigation of Ni-induced intoxication was confirmed via antioxidant and anti-apoptotic pathways and downregulation of NF-κB in the brain.