Zileuton Ameliorates Neuronal Ferroptosis and Functional Recovery After Spinal Cord Injury

Ferroptosis is a novel type of cell-death pattern characterized by iron-dependent, oxidative stress, and lipid peroxidation. Neurological pathology, especially in spinal cord injury (SCI), may involve a trace amount of ferroptosis. However, it's uncertain whether zileuton (ZIL), a selective 5-lipoxygenase (5-LO) inhibitor, can inhibit ferroptosis in SCI.

The study intended to investigate the etiology of neuronal ferroptosis and the ameliorative effects of ZIL against it for SCI mice.

The research team performed an animal study.

The study took place at the Fourth Affiliated Hospital of Harbin Medical University in Harbin, China.

The animals were adult, male, C57BL/6 mice, about 20 to 25 g in weight.

The research team: (1) stimulated HT22 cells, an immortalized mouse hippocampal neuronal cell line treated with erastin, and mice induced spinal cord trauma using a moderate hit, and (2) treated the cells and mice with ZIL.

The research team measured: (1) motor function, (2) neurological damage, (3) iron content, (4) lipid oxidation, and (5) neuroinflammation and glial response.

ZIL administration attenuated ferroptosis and lipid peroxidation in the HT22 cells. Moreover, ZIL mitigated the ferroptosis and inflammation in the injured spinal cords. Hence, ZIL can decrease neurological damage and improve recovery of motor function, indicating an ameliorative role for ZIL in SCI.

ZIL has anti-ferroptosis and anti-oxidative effects in neurons, which can contribute to recovery of motor function after induction of SCI. ZIL is a promising drug for inhibiting ferroptosis and protecting neurological functions after induction of SCI.