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Ebselen relieves ferroptosis induced by divalent mental transporter 1 in rats with subarachnoid hemorrhage



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Ebselen relieves ferroptosis induced by divalent mental transporter 1 in rats with subarachnoid hemorrhage


ZHANG Hongxia JIANG Dengzhi CHE Xudong ZHAO Qing ZHAO Jun XIANG Xiang HE Zhaohui

Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 40016, China


subarachnoid hemorrhage early brain injury ferroptosis divalent mental transporter ebselen


Objective       To investigate the expression of divalent mental transporter 1 (DMT1) and ferroptosis in rats after subarachnoid hemorrhage (SAH) and explore the neuroprotective effect of ebselen in association of inhibiting DMT1 against early brain injury after SAH.  Methods       Rat models of SAH were established by intravascular puncture. Immunofluorescence assay was used to identify the expression and location of DMT1 and glutathione peroxidase 4 (GPX4) in the brain cortex. Ebselen was administered by injection to the SAH. Western blotting was used to detect the expression of DMT and GPX4 at 72 h after the injury or after ebselen intervention. Intracellular iron deposition, iron content, and malonaldehyde (MDA) were measured to evaluate the ferroptosis. Neurological function and brain edema were observed to evaluate the early brain injury. Results    Immunofluorescence assay indentified DMT1 and GPX4 were both expressed in the cytoplasm of neurons in the brain cortex. Western blot results revealed that the expression level of DMT1 was increased then decreased in 24 h, and kept rising in 48 and 72 h after SAH injury (P<0.01), while that of GPX4 was decreased at 24 h, and then further reduced in 48 and 72 h (P<0.01). Compared with the SAH group and vehicle group, injections of 1, 2 and 4 mg/kg ebselen decreased the expression of DMT1 but increased that of GPX4, but significant differences were only found in the 2 and 4 mg/kg treatment groups (P<0.01). What’s more, 4 mg/kg ebselen also reduced iron deposition, iron and MDA contents (P<0.01), and elevated GSH content and GPX4 activity (P<0.01), and improved neurological function and augmented brain edema (P<0.01). Conclusion     Ebselen may decrease the intracellular iron transport through inhibiting the expression of DMT1, then decrease the ferroptosis, and thus exert protective effect on the early brain injury in rats after SAH.


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Last Update: 2017-08-20