Aluminum (Al) causes hippocampal lesions by oxidative stress, which is widely accepted as the primary pathogenesis of Al neurotoxicity. Lycopene (LYC), a naturally carotenoid, has received extensive attention due to its antioxidant effect. In this study, the neuroprotective effects and mechanisms of LYC against aluminum chloride (AlCl3)-induced hippocampal lesions were explored. First, oral administration of LYC (4 mg/kg) alleviated AlCl3-induced (150 mg/kg) cognition impairment and histopathological changes of the hippocampus in rats. Then, LYC significantly attenuated AlCl3-induced oxidative stress, presenting as the reduced reactive oxygen species, malondialdehyde and 8-hydroxy-2'-deoxyguanosine levels, and increased glutathione level and superoxide dismutase activity. Moreover, LYC also protected the hippocampus from AlCl3-induced apoptosis and neuroinflammation, as assessed by protein levels of p53, Bcl-2-associated X protein (Bax), B-cell lymphoma gene 2 (Bcl-2), Cytochrome c (Cyt c), cleaved caspase-3 and nuclear factor kappa B, as well as the mRNA levels of Bax, Bcl-2, tumor necrosis factor alpha, interleukin-6 and interleukin-1 beta. Finally, LYC increased nuclear factor-erythroid-2-related factor 2 (Nrf2) nuclear translocation and its downstream gene expression, including heme oxygenase-1, NAD(P)H: quinone oxidoreductase 1, glutamate cysteine ligase catalytic subunit and superoxide dismutase 1, which were involved in antioxidant, anti-apoptosis, and anti-inflammation. Overall, our findings demonstrate LYC attenuates Al-induced hippocampal lesions by inhibiting oxidative stress-mediated inflammation and apoptosis in the rat.
Keywords: Aluminum chloride； lycopene； hippocampal lesions；Nrf2；inflammation； apoptosis.
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