Deferasirox exerts anti-epileptic effects by improving brain iron homeostasis via regulation of ITPRIP.

Autor: Duan X; Department of Health Laboratory Technology, School of Public Health, Chongqing Medical University, Chongqing, 400016, China., Han H; Department of Health Laboratory Technology, School of Public Health, Chongqing Medical University, Chongqing, 400016, China., Liu J; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, 400016, China; Department of Neurology, Chongqing University Three Gorges Hospital, Chongqing, 404100, China., Qiu Y; Department of Neurology, University-Town Hospital of Chongqing Medical University, Chongqing, 401331, China., Wang Y; Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China., Wu X; Department of Clinical Laboratory, University-Town Hospital of Chongqing Medical University, Chongqing, 401331, China., Zhang H; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, 400016, China., Zou Z; Molecular Biology Laboratory of Respiratory Diseases, Institute of Life Sciences, Chongqing Medical University, Chongqing, 400016, China., Qiu J; Department of Health Laboratory Technology, School of Public Health, Chongqing Medical University, Chongqing, 400016, China., Chen C; Department of Occupational and Environmental Health, School of Public Health, Chongqing Medical University, Chongqing, 400016, China. Electronic address: chengzhichen@cqmu.edu.cn., Xiao F; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, 400016, China; Key Laboratory of Major Brain Disease and Aging Research（Ministry of Education), Chongqing Medical University, Chongqing, 400016, China. Electronic address: feixiao81@126.com., Tian X; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, 400016, China; Key Laboratory of Major Brain Disease and Aging Research（Ministry of Education), Chongqing Medical University, Chongqing, 400016, China. Electronic address: xintian@cqmu.edu.cn.
Jazyk: angličtina
Zdroj: Neurochemistry international [Neurochem Int] 2024 Jun; Vol. 176, pp. 105725. Date of Electronic Publication: 2024 Mar 30.
DOI: 10.1016/j.neuint.2024.105725
Abstrakt: Epilepsy constitutes a global health concern, affecting millions of individuals and approximately one-third of patients exhibit drug resistance. Recent investigations have revealed alterations in cerebral iron content in both epilepsy patients and animal models. However, the extant literature lacks a comprehensive exploration into the ramifications of modulating iron homeostasis as an intervention in epilepsy. This study investigated the impact of deferasirox, a iron ion chelator, on epilepsy. This study unequivocally substantiated the antiepileptic efficacy of deferasirox in a kainic acid-induced epilepsy model. Furthermore, deferasirox administration mitigated seizure susceptibility in a pentylenetetrazol-induced kindling model. Conversely, the augmentation of iron levels through supplementation has emerged as a potential exacerbating factor in the precipitating onset of epilepsy. Intriguingly, our investigation revealed a hitherto unreported discovery: ITPRIP was identified as a pivotal modulator of excitatory synaptic transmission, regulating seizures in response to deferasirox treatment. In summary, our findings indicate that deferasirox exerts its antiepileptic effects through the precise targeting of ITPRIP and amelioration of cerebral iron homeostasis, suggesting that deferasirox is a promising and novel therapeutic avenue for interventions in epilepsy.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier Ltd.)
Databáze: MEDLINE
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