• Clinics · Jan 2024

    Keap1/Nrf2 signaling pathway participating in the progression of epilepsy via regulation of oxidative stress and ferroptosis in neurons.

    • Dandan Wang, Yunmei Cui, Fan Gao, Weiwei Zheng, Jinzi Li, and Zhemin Xian.
    • Department of Ultrasound Medicine, Affiliated Hospital of Yanbian University, Yanji, Jilin, China.
    • Clinics (Sao Paulo). 2024 Jan 1; 79: 100372100372.

    ObjectiveThis study aims to analyze the relationship between the Kelch-like ECH-associated protein 1 (Keap1)/Nuclear factor-erythroid 2-related factor 2 (Nrf2) and Epilepsy (EP), as well as its mechanism of action.MethodsThirty Wistar rats were divided into a control group (without treatment), a model group (EP modeling), and an inhibition group (EP modeling + intervention by Keap1/Nrf2 signaling pathway inhibitor ATRA) and subject to Morris water maze experiment. Then, the expression of Oxidative Stress (OS) markers, ferroptosis-associated proteins and Keap1/Nrf2 pathway in rat hippocampus was measured. In addition, rat hippocampal neuronal cell HT22 was purchased and treated accordingly based on the results of grouping, and cell proliferation and apoptosis in the three groups were determined.ResultsCompared with rats in the model group, those in the inhibition group showed shorter escape latency and an increased number of platform crossings (p < 0.05). Significant OS and neuron ferroptosis, increased apoptosis rate, elevated Keap1 expression, and decreased Nrf2 expression were observed in the model group compared to the control group (p < 0.05). The inhibition group exhibited notably improved OS and ferroptosis, as well as enhanced neuronal viability (p < 0.05).ConclusionInhibition of the Keap1/Nrf2 pathway can reverse the OS and neuron viability in EP rats.Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.

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