Effects of Aluminum Oxide Nanoparticles in the Cerebrum, Hippocampus, and Cerebellum of Male Wistar Rats and Potential Ameliorative Role of Melatonin

Aluminum oxide nanoparticles (Al2O3 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 Al2O3 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), Al2O3 NP-treated (received 30 mg/kg body weight Al2O3 NPs), melatonin and Al2O3 NP-treated (received 30 mg/kg body weight Al2O3 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. Al2O3 NPs substantially increased malondialdehyde, ,g-amyloid 1-42 peptide, acetylcholinesterase, and ,g-secretase-1 expression, whereas they markedly decreased glutathione levels. Furthermore, Al2O3 NPs induced severe histopathological alterations, including vacuolation of the neuropil, enlarged pericellular and perivascular spaces, vascular congestion, neuronal degeneration, and pyknosis. Al2O3 NP treatment also resulted in an intense positive caspase-3 immunostaining. Conversely, the administration of melatonin alleviated the adverse effects induced by Al2O3 NPs. Therefore, melatonin can diminish the neurotoxic effects induced by Al2O3 NPs.