1. Academic Validation
  2. Propofol Inhibits Ferroptotic Cell Death Through the Nrf2/Gpx4 Signaling Pathway in the Mouse Model of Cerebral Ischemia-Reperfusion Injury

Propofol Inhibits Ferroptotic Cell Death Through the Nrf2/Gpx4 Signaling Pathway in the Mouse Model of Cerebral Ischemia-Reperfusion Injury

  • Neurochem Res. 2022 Nov 19. doi: 10.1007/s11064-022-03822-7.
Gui-Bo Fan 1 Yan Li 1 Gao-Shuo Xu 1 A-Yang Zhao 1 Hong-Jiang Jin 1 Si-Qi Sun 1 Si-Hua Qi 2
Affiliations

Affiliations

  • 1 Department of Anesthesiology, The 4th Affiliated Hospital of Harbin Medical University, 37 Yiyuan Road, Harbin, 150001, Heilongjiang, China.
  • 2 Department of Anesthesiology, The 4th Affiliated Hospital of Harbin Medical University, 37 Yiyuan Road, Harbin, 150001, Heilongjiang, China. [email protected].
Abstract

Ferroptosis is characterized by excessive accumulation of iron and lipid peroxides, which are involved in ischemia, reperfusion-induced organ injury, and stroke. Propofol, an anesthetic agent, has neuroprotective effects due to its potent antioxidant, anti-ischemic, and anti-inflammatory properties. However, the relationship between propofol and Ferroptosis is still unclear. In the current study, we elucidated the role of Ferroptosis in the neuroprotective effect of propofol in mouse brains subjected to cerebral ischemia reperfusion injury (CIRI). Ferroptosis was confirmed by Western blotting assays, transmission electron microscopy, and glutathione assays. Propofol regulated Nrf2/Gpx4 signaling, enhanced antioxidant potential, inhibited the accumulation of lipid peroxides in CIRI-affected neurons, and significantly reversed CIRI-induced Ferroptosis. Additionally, Gpx4 inhibitor RSL3 and Nrf2 inhibitor ML385 attenuated the effects of propofol on antioxidant capacity, lipid peroxidation, and Ferroptosis in CIRI-affected neurons. Our data support a protective role of propofol against Ferroptosis as a cause of cell death in mice with CIRI. Propofol protected against CIRI-induced Ferroptosis partly by regulating the Nrf2/Gpx4 signaling pathway. These findings may contribute to the development of future therapies targeting Ferroptosis induced by CIRI.

Keywords

Ferroptosis; Ischemic injury; Nrf2/Gpx4 signaling pathway; Propofol.

Figures
Products