Lycopene Prevents Phthalate-Induced Cognitive Impairment via Modulating Ferroptosis

Abstract

phthalate (DEHP) is frequently used as a plasticizer in industrial and agricultural products. DEHP can cause severe neurotoxicity, such as impaired learning and memory function. Lycopene (LYC) as a carotenoid exerts excellent antioxidant capacity and therapeutic effects in neurodegenerative diseases. However, whether LYC can prevent the cognitive impairment induced by DEHP and the specific mechanisms are unclear. In the present study, the behavioral test results suggested that LYC alleviated the learning and memory impairment induced by DEHP. The histopathological data revealed that LYC attenuated DEHP-induced disordered arrangement of the neurons in the CA1 and CA3 regions of the hippocampus tissue. Moreover, LYC inhibited the occurrence of DEHP-induced ferroptosis via regulating iron metabolism, inhibiting lipid peroxidation, and activating the cysteine transporter and nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (NrF2/HO-1) signaling pathway. Overall, the study contributes novel perspectives into the potential mechanisms of LYC preventing phthalate-induced cognitive impairment in the hippocampus.

Ferroptosis as an emerging target in sickle cell disease

“…( Schmidt et al, 2021 , Schmidt et al, 2023 ). This is mirrored in conditions like thalassemia and hereditary hemochromatosis ( Wang et al, 2017 , Ginwalla et al, 2018 , Sumneang et al, 2020 , Fujikura et al, 2022 , Wood, 2023 ), as well as in myocardial infarction, reperfusion injuries, and heart failure ( Fang et al, 2023 , Wang et al, 2023a ), highlighting a pattern of cardiac iron toxicity.…”

“…1 ) ( Wang et al, 2019 , Jiang et al, 2021 ). Across these diseases, ferroptosis-targeting treatments, including iron chelators and inhibitors of lipid peroxidation, show promise in reducing symptoms and slowing disease progression ( Wang et al, 2023a ). The essential role of lipid peroxides in immunity and inflammation, central to these diseases, highlights the need to determine whether the primary pathophysiological mechanisms in these conditions are governed by modulation of inflammation, ferroptosis, or an interplay of both ( Jiang et al, 2021 , Wang et al, 2023a ).…”

“…Elevated oxidative stress, mitochondrial iron overload, and dysregulation of the BACH1/HMOX1 axis contribute to ferroptosis. The involvement of GPX4 and the BACH1/ HMOX1 pathway in ferroptotic cell death may offer therapeutic targets, such as overexpressing SLC7A11 in cardiac cells to increase GSH levels and protect against ferroptosis in SCD ( Chen et al, 2023a , Wang et al, 2023a ).…”