Hydrogen Sulfide Sustained Release Donor Alleviates Spinal Cord Ischemia-Reperfusion-Induced Neuron Death by Inhibiting Ferritinophagy-Mediated Ferroptosis.

AIMS: Spinal cord ischemia-reperfusion injury (SCIRI) is a disastrous complication that cannot be completely prevented in thoracoabdominal aneurysm surgery, leading to sensory and motor dysfunction and even paraparesis, causing tremendous socioeconomic burden. Ferritinophagy is a form of autophagic ferroptosis, which is a contributor to SCIRI. Hydrogen sulfide (H(2)S) has been reported to be neuroprotective in various diseases. However, it remains unclear whether H(2)S alleviates SCIRI-induced neural death via regulating ferritinophagy-mediated ferroptosis. The aim of this study was to explore their relationship and interaction in SCIRI. RESULTS: The results demonstrate that Nissl bodies and motor function were obviously lost in SCIRI rats. Meanwhile, SCIRI led to a significant increase in DHE-positive neurons, TUNEL-positive neurons, LC3-positive neurons, and ferritin-positive neurons, downregulation of GPx4, Slc7a11, p62, and ferritin expression, and upregulation of LC3 II/I and NCOA4 expression. Additionally, there was upregulation of the level of MDA, GSH, and Fe(2+). Finally, we found that H(2)S could significantly relieve neuronal death and loss of motor function in SCIRI rats by inhibiting ferritinophagy and ferroptosis. CONCLUSION: Ferroptosis and ferritinophagy play a crucial role in the etiopathogenesis of SCIRI, and H(2)S exerts neuroprotection by inhibiting ferritinophagy-mediated ferroptosis.