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

• Published in: JOR-spine Vol. 7; no. 3; pp. e1344 - n/a
• Main Authors: Vahabi, Arman, Öztürk, Anıl Murat, Kılıçlı, Bünyamin, Birim, Derviş, Kaftan Öcal, Gizem, Dağcı, Taner, Armağan, Güliz
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.09.2024; Wiley
• Subjects: Cell culture; Cell death; Ferroptosis; iron chelation; Ketamine; Lipid peroxidation; Lipids; Monoclonal antibodies; neuroregeneration; Proteins; Spinal cord injuries; Istanbul Turkey; United States > US; Turkey; iron chelation; ferroptosis; neuroregeneration; lipid peroxidation
• ISSN: 2572-1143; 2572-1143
• DOI: 10.1002/jsp2.1344

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. Ferroptosis, which is a lately described iron‐dependent non‐apoptotic cell death, is shown to be influential in the pathogenesis of spinal cord injury. Silibinin is a potential therapeutic candidate possessing antiferroptotic properties in spinal cord injury model.