Abdelhameed_2023_ACS.Chem.Neurosci__

Aluminum oxide nanoparticles (Al(2)O(3) NPs) have been widely used in vaccine manufacture, food additives, human care products, and cosmetics. However, they also have adverse effects on different organs, including the liver, kidneys, and testes. Melatonin is a potent antioxidant, particularly against metals by forming melatonin-metal complexes. The present study aimed to investigate the protective effects of melatonin against Al(2)O(3) NP-induced toxicity in the rat brain. Forty adult male Wistar rats were allocated to four groups: the untreated control (received standard diet and distilled water), Al(2)O(3) NP-treated (received 30 mg/kg body weight Al(2)O(3) NPs), melatonin and Al(2)O(3) NP-treated (received 30 mg/kg body weight Al(2)O(3) NPs + 10 mg/kg body weight melatonin), and melatonin-treated (received 10 mg/kg body weight melatonin) groups. All treatments were by oral gavages and administered daily for 28 days. Afterward, the rats were sacrificed, and samples from various brain regions (cerebrum, cerebellum, and hippocampus) were subjected to biochemical, histopathological, and immunohistochemical analyses. Al(2)O(3) NPs substantially increased malondialdehyde, beta-amyloid 1-42 peptide, acetylcholinesterase, and beta-secretase-1 expression, whereas they markedly decreased glutathione levels. Furthermore, Al(2)O(3) NPs induced severe histopathological alterations, including vacuolation of the neuropil, enlarged pericellular and perivascular spaces, vascular congestion, neuronal degeneration, and pyknosis. Al(2)O(3) NP treatment also resulted in an intense positive caspase-3 immunostaining. Conversely, the administration of melatonin alleviated the adverse effects induced by Al(2)O(3) NPs. Therefore, melatonin can diminish the neurotoxic effects induced by Al(2)O(3) NPs.