Unveiling the shield: Troglitazone's impact on epilepsy‐induced nerve injury through ferroptosis inhibition

作者：Zhibin Wang, Junyan Liu, Shilong Jiang, Wei Zhuo, Pan Xie, Wenting Dai, Xiao‐Yuan Mao, Zhaoqian Liu · 发表于：CNS Neuroscience & Therapeutics · 年份：2024 · DOI：10.1111/cns.14911 · 被引用次数：11 · 研究领域：Ferroptosis and cancer prognosis、Cholesterol and Lipid Metabolism、Cancer, Lipids, and Metabolism

BACKGROUND: Epilepsy is a widespread central nervous system disorder with an estimated 50 million people affected globally. It is characterized by a bimodal incidence peak among infants and the elderly and is influenced by a variety of risk factors, including a significant genetic component. Despite the use of anti-epileptic drugs (AEDs), drug-refractory epilepsy develops in about one-third of patients, highlighting the need for alternative therapeutic approaches. AIMS: The primary aim of this study was to evaluate the neuroprotective effects of troglitazone (TGZ) in epilepsy and to explore the potential mechanisms underlying its action. METHODS: We employed both in vitro and in vivo models to assess TGZ's effects. The in vitro model involved glutamate-induced toxicity in HT22 mouse hippocampal neurons, while the in vivo model used kainic acid (KA) to induce epilepsy in mice. A range of methods, including Hoechst/PI staining, CCK-8 assay, flow cytometry, RT-PCR analysis, Nissl staining, scanning electron microscopy, and RNA sequencing, were utilized to assess various parameters such as cellular damage, viability, lipid-ROS levels, mitochondrial membrane potential, mRNA expression, seizure grade, and mitochondrial morphology. RESULTS: Our results indicate that TGZ, at doses of 5 or 20 mg/kg/day, significantly reduces KA-induced seizures and neuronal damage in mice by inhibiting the process of ferroptosis. Furthermore, TGZ was found to prevent changes in mitochondrial morpholog...