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UAMC-3203 inhibits ferroptosis and promotes functional recovery in rats with spinal cord injury.
Kan, Shunli; Feng, Sa; Zhao, Xinyan; Chen, Ziyu; Zhou, Mengmeng; Liu, Linyan; Zhu, Haoqiang; Cheng, Yuelin; Fu, Xuanhao; Hu, Wei; Zhu, Rusen.
Afiliación
  • Kan S; Department of Spine Surgery, Tianjin Union Medical Center, Tianjin, China.
  • Feng S; Tianjin Institute of Spinal Surgery, Tianjin, China.
  • Zhao X; Department of Spine Surgery, Tianjin Union Medical Center, Tianjin, China.
  • Chen Z; Tianjin Institute of Spinal Surgery, Tianjin, China.
  • Zhou M; Department of Spine Surgery, Tianjin Union Medical Center, Tianjin, China.
  • Liu L; Tianjin Institute of Spinal Surgery, Tianjin, China.
  • Zhu H; Department of Spine Surgery, Tianjin Union Medical Center, Tianjin, China.
  • Cheng Y; Tianjin Institute of Spinal Surgery, Tianjin, China.
  • Fu X; Department of Spine Surgery, Tianjin Union Medical Center, Tianjin, China.
  • Hu W; Tianjin Institute of Spinal Surgery, Tianjin, China.
  • Zhu R; Department of Spine Surgery, Tianjin Union Medical Center, Tianjin, China.
Sci Rep ; 14(1): 20180, 2024 08 30.
Article en En | MEDLINE | ID: mdl-39215144
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Traumatismos de la Médula Espinal / Recuperación de la Función / Factor 2 Relacionado con NF-E2 / Ferroptosis Límite: Animals Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Traumatismos de la Médula Espinal / Recuperación de la Función / Factor 2 Relacionado con NF-E2 / Ferroptosis Límite: Animals Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido