Ferrostatin-1 (Fer-1), known for its potent inhibition of ferroptosis, effectively blocks the ferroptosis triggered by Erastin in HT-1080 cells, with an EC50 value of 60 nM. As a synthetic antioxidant, Ferrostatin-1 operates through a reductive action to shield membrane lipids from damage, thus preventing cellular death. Additionally, it demonstrates antifungal properties[1][2][3]. Ferrostatin-1 thwarts the build-up of cytosolic and lipid reactive oxygen species (ROS) caused by erastin. It also protects against glutamate-triggered neurotoxicity in organotypic slices of rat brain[1]. At a concentration of 2 μM for 24 hours, Ferrostatin-1 safeguards against neurotoxicity induced by 5 mM Glutamate in rat organotypic hippocampal slice cultures (OHSC). While Ferrostatin-1 impedes lipid peroxidation, it does not affect the formation of mitochondrial ROS or the permeability of lysosomal membranes. It also prevents cell death in models of Huntington's disease (HD), periventricular leukomalacia (PVL), and kidney dysfunction[2]. At a dosage of 1 μM over 6 hours, Ferrostatin-1 hinders the oxidative degradation of unsaturated fatty acids in HT-1080 cells, leading to an increase in the count of healthy medium spiny neurons (MSNs)[3].
Ferrostatin-1 动物研究
Animal study
Administered at a dosage of 5 mg/kg intraperitoneally (ip), as a single dose 30 minutes prior to glycerol injection, Ferrostatin-1 enhances renal function in mice suffering from rhabdomyolysis. This improvement was not seen with the pan-caspase inhibitor zVAD or in mice lacking RIPK3[1]. When given via tail vein injection at 0.8 mg/kg, Ferrostatin-1 significantly mitigates LPS-induced acute lung injury (ALI)[4]. Additionally, Ferrostatin-1, at a dose of 5 mg/kg ip in C57BL/6J mice, benefits renal function in rhabdomyolysis conditions[5]. Moreover, Ferrostatin-1 administered at 10 mg/kg/day ip for 3 days reduces hypoxic-ischemic brain damage, oxygen-glucose deprivation, and Erastin-induced ferroptosis in the brains of neonatal rats[6]. Lastly, at a dose of 0.655 mg/kg ip, administered three times weekly for six weeks, Ferrostatin-1 displays anti-ferroptosis properties by boosting GPX4 activity and inhibiting lipid peroxidation in the salivary glands of ovariectomized rats, a model for postmenopause[7].
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