Cottonseed oil alleviates ischemic stroke injury by inhibiting ferroptosis

作者：Miao Sun, Min Liu, Qingxiao Li, Xiaoying Zhang, Siyuan Liu, Huikai Yang, Le Yang, Jiahe Tian, Weidong Mi, Yulong Ma · 发表于：Brain and Behavior · 年份：2023 · DOI：10.1002/brb3.3179 · 被引用次数：27 · 研究领域：Ferroptosis and cancer prognosis、Trace Elements in Health、Retinoids in leukemia and cellular processes

INTRODUCTION: Ferroptosis has recently been recognized as a new cause of ischemia reperfusion injury due to blood-brain barrier (BBB) disruption followed by secondary iron-loaded transferrin (TF) influx. As a novel and independent cell death pathway, ferroptosis was characterized by iron-dependent lipid peroxidation, decline of GSH, GPX4, and shrinking mitochondria. Cottonseed oil (CSO), a liposoluble solvent, can alleviate ischemia stroke injuries and oxidative stress. However, the effect of CSO on ischemic stroke-induced ferroptosis has not been explored. In this study, we investigated the effect of CSO on ferroptosis caused by cerebral ischemic injury in rats. METHODS: Ga-citrate PET, Western blot, immunofluorescence staining, Elisa kits, and transmission electron microscopy to detect the infarct volume, neural injuries, and ferroptosis-related indexes. RESULTS: CSO treatment could significantly ameliorate MCAO-R-induced neurological dysfunction in a male rat model. Furthermore, it reduced infarct volume and neuronal injuries; protected BBB integrity; reduced the influx of iron ion, TF, and TF receptors; up-regulated anti-ferroptosis proteins (GPX4, xCT, HO1, FTH1), while down-regulating ferroptosis-related protein ACSL4; increased the activity of GSH and SOD; and decreased MDA and LPO levels. Mitochondrial destruction induced by ischemic stroke was also alleviated by CSO treatment. CONCLUSION: CSO treatment can alleviate ischemic stroke injury via ferroptosis inhibition, ...