Silibinin promotes healing in spinal cord injury through anti-ferroptotic mechanisms

IF 3.4 3区 医学 Q1 ORTHOPEDICS JOR Spine Pub Date : 2024-07-01 DOI:10.1002/jsp2.1344
Arman Vahabi, Anıl Murat Öztürk, Bünyamin Kılıçlı, Derviş Birim, Gizem Kaftan Öcal, Taner Dağcı, Güliz Armağan
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Abstract

Study Design

Pre-clinical animal experiment.

Objective

In this study, we investigated therapeutic effects of silibinin in a spinal cord injury (SCI) model. In SCI, loss of cells due to secondary damage mechanisms exceeds that caused by primary damage. Ferroptosis, which is iron-dependent non-apoptotic cell death, is shown to be influential in the pathogenesis of SCI.

Methods

The study was conducted as an in vivo experiment using a total of 78 adult male/female Sprague Dawley rats. Groups were as follows: Sham, SCI, deferoxamine (DFO) treatment, and silibinin treatment. There were subgroups with follow-up periods of 24 h, 72 h, and 6 weeks in all groups. Malondialdehyde (MDA), glutathione (GSH), and Fe2+ levels were measured by spectrophotometry. Glutathione peroxidase-4 (GPX4), ferroportin (FPN), transferrin receptor (TfR1), and 4-hydroxynonenal (4-HNE)-modified protein levels were assessed by Western blotting. Functional recovery was assessed using Basso–Beattie–Bresnahan test.

Results

Silibinin achieved significant suppression in MDA and 4-HNE levels compared to the SCI both in 72-h and 6 weeks group (p < 0.05). GSH, GPX4, and FNP levels were found to be significantly higher in the silibinin 24 h, 72 h, and 6 weeks group compared to corresponding SCI groups (p < 0.05). Significant reduction in iron levels was observed in silibinin treated rats in 72 h and 6 weeks group (p < 0.05). Silibinin substantially suppressed TfR1 levels in 24 h and 72 h groups (p < 0.05). Significant difference among recovery capacities was observed as follows: Silibinin > DFO > SCI (p < 0.05).

Conclusion

Impact of silibinin on iron metabolism and lipid peroxidation, both of which are features of ferroptosis, may contribute to therapeutic activity. Within this context, our findings posit silibinin as a potential therapeutic candidate possessing antiferroptotic properties in SCI model. Therapeutic agents capable of effectively and safely mitigating ferroptotic cell death hold the potential to be critical points of future clinical investigations.

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Silibinin 通过抗发炎机制促进脊髓损伤的愈合。
研究设计临床前动物实验:本研究调查了西利宾在脊髓损伤(SCI)模型中的治疗效果。在脊髓损伤(SCI)中,继发性损伤机制造成的细胞损失超过了原发性损伤造成的细胞损失。铁凋亡是一种铁依赖性非凋亡性细胞死亡,在 SCI 的发病机制中具有重要影响:研究以体内实验的形式进行,共使用 78 只成年雄性/雌性 Sprague Dawley 大鼠。分组如下SCI、去氧胺(DFO)治疗和西利宾治疗。所有组别均设有随访期为 24 小时、72 小时和 6 周的子组。用分光光度法测量丙二醛(MDA)、谷胱甘肽(GSH)和 Fe2+ 的水平。谷胱甘肽过氧化物酶-4(GPX4)、铁蛋白(FPN)、转铁蛋白受体(TfR1)和 4-羟基壬烯醛(4-HNE)修饰蛋白水平通过 Western 印迹法进行评估。采用巴索-巴蒂-布雷斯纳汉试验评估功能恢复情况:结果:与 SCI 相比,西利宾在 72 小时组和 6 周组的 MDA 和 4-HNE 水平都有明显的抑制作用(p p p p DFO > SCI(p 结论:西利宾在 72 小时组和 6 周组的 MDA 和 4-HNE 水平都有明显的抑制作用(p p p DFO > SCI):西利宾对铁代谢和脂质过氧化的影响(两者都是铁变态反应的特征)可能有助于治疗活动。在这种情况下,我们的研究结果表明,西利宾是一种潜在的候选治疗药物,在 SCI 模型中具有抗铁细胞减少的特性。能够有效、安全地减轻铁变态反应细胞死亡的治疗药物有可能成为未来临床研究的关键点。
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来源期刊
JOR Spine
JOR Spine ORTHOPEDICS-
CiteScore
6.40
自引率
18.90%
发文量
42
审稿时长
10 weeks
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