Potential Risk of Choline Alfoscerate on Isoflurane-Induced Toxicity in Primary Human Astrocytes.

IF 1.4 4区 医学 Q4 CLINICAL NEUROLOGY
Journal of Korean Neurosurgical Society Pub Date : 2024-07-01 Epub Date: 2023-10-20 DOI:10.3340/jkns.2023.0208
Hyun Jung Lee, Hye Rim Cho, Minji Bang, Yeo Song Lee, Youn Jin Kim, Kyuha Chong
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引用次数: 0

Abstract

Objective: Isoflurane, a widely used common inhalational anesthetic agent, can induce brain toxicity. The challenge lies in protecting neurologically compromised patients from neurotoxic anesthetics. Choline alfoscerate (L-α-Glycerophosphorylcholine, α-GPC) is recognized for its neuroprotective properties against oxidative stress and inflammation, but its optimal therapeutic window and indications are still under investigation. This study explores the impact of α-GPC on human astrocytes, the most abundant cells in the brain that protect against oxidative stress, under isoflurane exposure.

Methods: This study was designed to examine changes in factors related to isoflurane-induced toxicity following α-GPC administration. Primary human astrocytes were pretreated with varying doses of α-GPC (ranging from 0.1 to 10.0 μM) for 24 hours prior to 2.5% isoflurane exposure. In vitro analysis of cell morphology, water-soluble tetrazolium salt-1 assay, quantitative real-time polymerase chain reaction, proteome profiler array, and transcriptome sequencing were conducted.

Results: A significant morphological damage to human astrocytes was observed in the group that had been pretreated with 10.0 mM of α-GPC and exposed to 2.5% isoflurane. A decrease in cell viability was identified in the group pretreated with 10.0 μM of α-GPC and exposed to 2.5% isoflurane compared to the group exposed only to 2.5% isoflurane. Quantitative real-time polymerase chain reaction revealed that mRNA expression of heme-oxygenase 1 and hypoxia-inducible factor-1α, which were reduced by isoflurane, was further suppressed by 10.0 μM α-GPC pretreatment. The proteome profiler array demonstrated that α-GPC pretreatment influenced a variety of factors associated with apoptosis induced by oxidative stress. Additionally, transcriptome sequencing identified pathways significantly related to changes in isoflurane-induced toxicity caused by α-GPC pretreatment.

Conclusion: The findings suggest that α-GPC pretreatment could potentially enhance the vulnerability of primary human astrocytes to isoflurane-induced toxicity by diminishing the expression of antioxidant factors, potentially leading to amplified cell damage.

氯化胆碱对异氟醚诱导的原代人类星形胶质细胞毒性的潜在风险。
目的:异氟醚是一种应用广泛的常用吸入麻醉药,可引起脑毒性。挑战在于保护神经系统受损的患者免受神经毒性麻醉剂的伤害。半焦胆碱(L-α-甘油磷酸胆碱,α-GPC)因其对氧化应激和炎症的神经保护特性而被公认,但其最佳治疗窗口和适应症仍在研究中。本研究探讨了在异氟烷暴露下,α-GPC对人类星形胶质细胞的影响,星形胶质细胞是大脑中最丰富的保护氧化应激的细胞。方法:本研究旨在检测α-GPC给药后异氟烷毒性相关因素的变化。在2.5%异氟烷暴露前,用不同剂量的α-GPC(0.1至10.0μM)预处理原代人类星形胶质细胞24小时。进行了细胞形态的体外分析、水溶性四氮唑盐-1测定、定量实时聚合酶链反应、蛋白质组轮廓仪阵列和转录组测序。结果:在用10.0mMα-GPC预处理并暴露于2.5%异氟烷的组中,观察到对人类星形胶质细胞的显著形态学损伤。与仅暴露于2.5%异氟醚的组相比,用10.0μMα-GPC预处理并暴露于2.5%异氟烷的组的细胞活力降低。定量实时聚合酶链反应显示,10.0μMα-GPC预处理进一步抑制了异氟烷降低的血红素加氧酶1和缺氧诱导因子-1α的mRNA表达。蛋白质组轮廓仪阵列表明,α-GPC预处理影响了与氧化应激诱导的细胞凋亡相关的多种因素。此外,转录组测序确定了与α-GPC预处理引起的异氟醚诱导毒性变化显著相关的途径。结论:研究结果表明,α-GPC预处理可能通过减少抗氧化因子的表达,增强原代人星形胶质细胞对异氟醚诱导的毒性的脆弱性,从而可能导致细胞损伤扩大。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
2.90
自引率
6.20%
发文量
109
审稿时长
3-8 weeks
期刊介绍: The Journal of Korean Neurosurgical Society (J Korean Neurosurg Soc) is the official journal of the Korean Neurosurgical Society, and published bimonthly (1st day of January, March, May, July, September, and November). It launched in October 31, 1972 with Volume 1 and Number 1. J Korean Neurosurg Soc aims to allow neurosurgeons from around the world to enrich their knowledge of patient management, education, and clinical or experimental research, and hence their professionalism. This journal publishes Laboratory Investigations, Clinical Articles, Review Articles, Case Reports, Technical Notes, and Letters to the Editor. Our field of interest involves clinical neurosurgery (cerebrovascular disease, neuro-oncology, skull base neurosurgery, spine, pediatric neurosurgery, functional neurosurgery, epilepsy, neuro-trauma, and peripheral nerve disease) and laboratory work in neuroscience.
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