UAMC-3203 inhibits ferroptosis and promotes functional recovery in rats with spinal cord injury (vol 14, 20180, 2024)

被引：0

作者：

Kan, Shunli ^{[1
]}

Feng, Sa ^{[1
]}

Zhao, Xinyan ^{[1
]}

Chen, Ziyu ^{[1
]}

Zhou, Mengmeng ^{[1
]}

Liu, Linyan ^{[1
]}

Zhu, Haoqiang ^{[1
]}

Cheng, Yuelin ^{[1
]}

Fu, Xuanhao ^{[1
]}

Hu, Wei ^{[1
]}

Zhu, Rusen ^{[1
]}

机构：

[1] Tianjin Med Univ, Tianjin Union Med Ctr, Dept Spine Surg, Tianjin, Peoples R China

来源：

SCIENTIFIC REPORTS | 2024年 / 14卷 / 01期

关键词：

Ferroptosis; Neuroinflammation; Neuroprotection; Spinal cord injury; UAMC-3203;

D O I：

10.1038/s41598-024-78546-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Spinal cord injury (SCI) results in irreversible neurological impairment. After SCI, Ferritinophagy-induced free iron released from ferritin can lead to extensive lipid peroxidation and aggravate neurological damage. NRF2/HO-1 pathway is to endow cells with a protective effect against oxidative stress, and it plays an important role in the transcriptional activation of a series of antioxidant and detoxification genes. UAMC-3203 is a ferrostatin-1(Fer-1) analogue with better solubility and stability, which can more effectively inhibit ferroptosis after SCI. A rat SCI model was constructed, and the recovery of motor function was observed after treatment with UAMC-3203. ELISA was employed to assess the impact of UAMC-3203 on inflammation-related factors, while immunofluorescence was utilized to investigate the influence of UAMC-3203 on neuronal count as well as the activation of astrocytes and microglia/macrophages. Malondialdehyde (MDA) were detected to reflect the level of oxidation products. Western blot analysis was used to measure the level of ferroptosis markers and the expression of NRF2/HO-1. Our findings demonstrate that UAMC-3203 inhibits the production of reactive oxygen species (ROS) and lipid peroxides, preventing ferroptosis and reducing neuronal degeneration. Additionally, UAMC-3203 suppresses astrocyte proliferation and microglia/macrophage activation, as well as the release of ferroptosis-related inflammatory factors. These combined effects contribute to the preservation of spinal cord tissue and the facilitation of motor function recovery. UAMC-3203 maybe inhibit ferroptosis after SCI to promote functional recovery.

引用

页数：1