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 细胞实验
Cell Line
Concentration
Treated Time
Description
References
RD cells
100 μM
36 h
Inhibited lipid peroxidation and cell death induced by CV-A6 infection
mBio. 2022 Feb 22;13(1):e0271721.
EA.hy926 cells
1 μM
24 h
Inhibited ZnONPs-induced cell death and lipid peroxidation
Autophagy. 2021 Dec;17(12):4266-4285.
HUVECs
1 μM
24 h
Inhibited ZnONPs-induced cell death and lipid peroxidation
Autophagy. 2021 Dec;17(12):4266-4285.
A549 cells
2 μM
2 hours
To investigate the effect of iFSP1 on PAM-induced ferroptosis, results showed that iFSP1 enhanced PAM-induced ferroptosis.
Cell Death Dis. 2022 Mar 7;13(3):212.
H1299 cells
2 μM
2 hours
To investigate the effect of iFSP1 on PAM-induced ferroptosis, results showed that iFSP1 enhanced PAM-induced ferroptosis.
Cell Death Dis. 2022 Mar 7;13(3):212.
H9C2 cells
2 μM
reduced DOX-induced cell death by approximately 50%
Redox Biol. 2023 Sep;65:102825.
H9C2 cells
2 μM
fully rescued erastin-induced cell death
Redox Biol. 2023 Sep;65:102825.
mouse primary microglial cells (mPMs)
10 μM
1 h
Inhibited HIV-1 Tat-mediated microglial ferroptosis, reduced lipid peroxidation and the release of proinflammatory cytokines.
Redox Biol. 2023 Jun;62:102689.
FHs74Int cells
5 μM
120 h
Fer-1 significantly reduced IR-induced cell death and lipid peroxidation levels in the presence of AA
Redox Biol. 2023 Oct;66:102857.
FHs74Int cells
5 μM
72 h
Fer-1 significantly reduced IR-induced lipid peroxidation levels in the presence of AA
To explore whether E-Exe preconditioning of PAMCs could resist DIC injury-induced ferroptosis, results showed that Fer-1 significantly alleviated DIC injury
Redox Biol. 2024 Apr;70:103079.
HTR-8/SVneo cells
5 μM
36 h
Blocking ferroptosis significantly reversed the shFTL-induced decrease in cell viability and improved the changes in most ferroptotic marker concentrations/activities.
Redox Biol. 2022 Dec;58:102555.
L02 cells
5 μM
1 h
Fer-1 pretreatment significantly increased the protein expression of GPX4 and Ferritin, restored the decreased GSH levels and elevated MDA content caused by EC treatment, and alleviated the cytotoxicity induced by EC.
Redox Biol. 2022 Jul;53:102349.
NRK49F cells
5 μM
1 h
Restored GPX4 protein expression
Cell Death Dis. 2023 Feb 2;14(2):78.
HK-2 cells
5 μM
1 h
Restored GPX4 protein expression
Cell Death Dis. 2023 Feb 2;14(2):78.
VSC4.1 cell line
1 μM
12 h
To evaluate the protective effect of Ferrostatin-1 on RSL3-induced cell death, it was found that Ferrostatin-1 significantly increased cell viability
Bioact Mater. 2024 May 12;38:438-454.
HT22 cell line
1 μM
12 h
To evaluate the protective effect of Ferrostatin-1 on RSL3-induced cell death, it was found that Ferrostatin-1 significantly increased cell viability
Bioact Mater. 2024 May 12;38:438-454.
Huc-MSCs
1 μM
24 h
To evaluate the effect of Ferrostatin-1 on RSL3-induced intracellular GSH levels, it was found that Ferrostatin-1 significantly increased GSH levels
Bioact Mater. 2024 May 12;38:438-454.
NRK49F cells
1 μM
1 h
Used to inhibit cell death induced by CMPF. The results showed that pretreatment with Ferrostatin-1 significantly reduced ROS production induced by CMPF
Cell Death Dis. 2023 Feb 2;14(2):78.
HK-2 cells
1 μM
1 h
Used to inhibit cell death induced by CMPF. The results showed that pretreatment with Ferrostatin-1 significantly reduced ROS production induced by CMPF
Cell Death Dis. 2023 Feb 2;14(2):78.
ZR-75-1
10 µM
1 h
Fer-1 significantly attenuated IR-induced cell death in ER-positive ZR-75-1 cells
Front Cell Dev Biol. 2022 Feb 16;9:772380.
MCF-7
10 µM
1 h
Fer-1 significantly attenuated IR-induced cell death in ER-positive MCF-7 and ZR-75-1, but not in ER-negative MDA-MB-231 cells
Front Cell Dev Biol. 2022 Feb 16;9:772380.
LLC-MK2 cells
40 μM
2-5 days
Inhibited lipid peroxidation induced by CoV-229E infection
mBio. 2022 Feb 22;13(1):e0271721.
oligodendrocytes (OLs)
100 nM
Protected oligodendrocytes from cystine deprivation-induced death
J Am Chem Soc. 2014 Mar 26;136(12):4551-6.
HT-1080 fibrosarcoma cells
1 μM
7.5 h
Inhibited erastin-induced lipid peroxidation and cell death
J Am Chem Soc. 2014 Mar 26;136(12):4551-6.
BMSCs
10 μM
12 h
To evaluate the inhibitory effect of Ferrostatin-1 on bacteria-induced ferroptosis in BMSCs. Results showed that Fer-1 significantly reduced the mortality rate of BMSCs and decreased the accumulation of lipid peroxides and ferrous ions.
Adv Sci (Weinh). 2024 Oct;11(39):e2404453.
LO2 cells
10 μM
24 h
Inhibited ferroptosis and alleviated CM-IH-induced lipid accumulation and ferroptosis phenotype
Adv Sci (Weinh). 2024 Nov;11(41):e2402241.
HepG2 cells
10 μM
24 h
Inhibited ferroptosis and alleviated CM-IH-induced lipid accumulation and ferroptosis phenotype
Adv Sci (Weinh). 2024 Nov;11(41):e2402241.
human monocyte-derived macrophages
10 µM
4 days
inhibited Mtb-induced macrophage necrosis and lipid peroxidation
J Exp Med. 2019 Mar 4;216(3):556-570.
murine bone marrow-derived macrophages (BMDMs)
10 µM
4 days
inhibited Mtb-induced macrophage necrosis and lipid peroxidation
J Exp Med. 2019 Mar 4;216(3):556-570.
Ferrostatin-1 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
DOX-induced cardiomyopathy model
Subcutaneous injection
1 mg/kg
Daily for 7 days
Significantly rescued DOX-induced cardiac dysfunction, fibrosis, and oxidative stress
Redox Biol. 2023 Sep;65:102825.
C57BL/6J mice
Radiation-induced intestinal injury model
Intraperitoneal injection
5 mg/kg
Once daily for 14 days
Fer-1 significantly improved the survival rate of mice and alleviated radiation-induced intestinal fibrosis
Redox Biol. 2023 Oct;66:102857.
Mice
Bone cancer pain model
Intraperitoneal injection
10 mg/kg
Once daily for 20 consecutive days
FER-1 alleviated mechanical allodynia and thermal hyperalgesia in a mouse model of bone cancer pain and reduced spontaneous pain behavior. Furthermore, FER-1 inhibited the pain-associated activation of ERK1/2 and COX-2 expression and prevented the loss of GABAergic interneurons.
Redox Biol. 2023 Jun;62:102700
Mice
Doxorubicin-induced cardiotoxicity (DIC) model
Intraperitoneal injection
1 mg/kg
Once daily for 2 weeks
To explore the influence of ferroptosis induced by DIC injury on E-Exe preconditioning, results showed that Fer-1 significantly alleviated DIC injury
Redox Biol. 2024 Apr;70:103079.
Rats
FTL knockdown pregnant rat model
Intraperitoneal injection
2 μM/kg
Every two days until GD17.5
Blocking ferroptosis significantly reversed the shFTL-induced PE-like phenotypes, including improvements in glomerular morphological damage, 24-hour proteinuria, and blood pressure.
Redox Biol. 2022 Dec;58:102555.
Balb/c mice
EC-induced liver injury model
Intraperitoneal injection
1 mg/kg
21 consecutive days
Fer-1 pretreatment significantly increased and liver index in mice, decreased serum AST and ALT levels, alleviated EC-induced liver inflammation and oxidative stress, and restored the protein expression of GPX4 and Ferritin.
To evaluate the inhibitory effect of Ferrostatin-1 on bacteria-induced ferroptosis in BMSCs in vivo. Results showed that Fer-1 significantly reduced the levels of lipid peroxides in BMSCs.
Adv Sci (Weinh). 2024 Oct;11(39):e2404453.
C57BL/6 mice
NAFLD model induced by high-fat diet and chronic intermittent hypoxia
Intraperitoneal injection
1 mg/kg
Once daily for four weeks
Inhibited ferroptosis and alleviated HFD and CIH-induced liver function injury and lipid accumulation
Adv Sci (Weinh). 2024 Nov;11(41):e2402241.
C57BL/6 mice
Mtb H37Rv infection model
Intraperitoneal injection
3 mg/kg
Once daily from day 15 to day 28 post-infection
Reduced pulmonary necrosis and bacterial load
J Exp Med. 2019 Mar 4;216(3):556-570.
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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