The investigation of the effect of ethanol on ferroptosis-associated NRF2/GPx4 pathway in rats with spinal cord injury

Ethanol use is found in approximately one-third of spinal cord injury cases. However, the effect of ethanol on the physiopathological processes in spinal cord injury is not well understood. After spinal cord injury, the increase in iron load with bleeding at the trauma site and the rich lipid content of the spinal tissue provide a favorable environment for ferroptosis. There is no study in the literature demonstrating the effect of ethanol on ferroptosis mechanisms in spinal cord injury. Therefore, in our study, a spinal cord injury model was created in rats after ethanol administration and biochemical and histopathological examinations related to ferroptosis NRF2/GPx4 pathway were performed 1 hour later. When the findings were analyzed, no statistically significant change was observed in NRF2 gene expression between the groups. When evaluating the main regulatory SLC7A11/GPx4/GSH pathway of ferroptosis, it was observed that in addition to the pathway being suppressed in the groups where ethanol was administered or spinal cord injury was performed, the pathway was more significantly suppressed in the group where spinal cord injury was performed after ethanol administration. When evaluating lipid peroxidation products, consistent with the suppression of the SLC7A11/GPx4/GSH pathway, the levels of 4-HNE and MDA were significantly higher in the spinal cord injury following ethanol administration in rats. Hematoxylin-Eosin, Nissl staining and TEM analyses showed that neuronal damage and characteristic signs of ferroptosis were more pronounced in spinal cord injury after ethanol administration, consistent with biochemical findings. In conclusion, our study shows that ferroptotic damage is more severe and occurs as early as 1 hour in spinal cord injury at high blood alcohol concentrations.