Table 1:
Potential Oxytosis/Ferroptosis Inhibitors
| Compound | Target | 5 mM glutamate | 500 nM erastin | 250 nM RSL3 |
|---|---|---|---|---|
| No treatment | 7.3 ± 4.3% | 6.5 ± 3.7% | 7.2 ± 6.9% | |
| Ferrostatin (10 μM) | Lipid perox. | 83.1 ± 4.0%**** | 82.6 ± 2.7%**** | 84.7 ± 3.3%**** |
| Liproxstatin (1 μM) | Lipid perox. | 75.1 ± 5.7%**** | 71.5 ± 4.4%**** | 81.9 ± 1.5%**** |
| Deferiprone (100 μM) | Fe chelator | 90.0 ± 5.0%**** | 93.2 ± 2.7%**** | 87.8 ± 3.7%**** |
| MitoQ (1 μM) | mitochondria | 90.9 ± 13.0%**** | 76.8 ± 6.9%**** | 102.8 ± 13.4%**** |
| Clorgyline (100 μM) | mitochondria | 86.4 ± 8.7%**** | 86.0 ± 4.7%**** | 95.4 ± 7.1%**** |
| 968 (10 μM) | mitochondria | 88.4 ± 1.4%**** | 70.3 ± 1.1%**** | 79.5 ± 8.3%**** |
| AOA (1 mM) | mitochondria | 79.0 ± 4.2%**** | 78.3 ± 8.3%**** | 1.5 ± 0.2% |
| GSK2795039 (10 μM) | NOX2 | 78.1 ± 0.5%**** | 71.7 ± 1.7%**** | 87.5 ± 1.7%**** |
| GKT137831 (10 μM) | NOX1/4 | 63.7 ± 6.6%**** | 64.2 ± 5.0%**** | 90.0 ± 2.4%**** |
| PD146176 (5 μM) | 15LOX | 83.9 ± 0.6%**** | 88.9 ± 7.5%**** | 87.4 ± 1.5%**** |
| Troglitazone (1 μM) | ACSL4 | 76.5 ± 4.4%**** | 70.3 ± 4.2%**** | 96.8 ± 4.0%**** |
| Idebenone (1 μM) | FSP1 | 70.2 ± 5.3%**** | 68.9 ± 4.2%**** | 91.7 ± 7.7%**** |
| CoCl2 (100 μM) | Calcium influx | 77.8 ± 1.1%**** | 72.9 ± 4.0%**** | 76.4 ± 6.8%**** |
| LY83583 (1 μM) | Calcium influx | 76.0 ± 2.6%**** | 81.1 ± 2.6%**** | 91.2 ± 1.3%**** |
| Apomorphine (5 μM) | Calcium influx | 86.9 ± 1.0%**** | 78.6 ± 7.2%**** | 90.7 ± 4.2%**** |
| BI-6C9 (10 μM) | Bid inhib. | 84.7 ± 2.5%**** | 78.7 ± 8.1%**** | 90.9 ± 1.0%**** |
| Bafilomycin (100 nM) | Autophagy | 88.7 ± 1.3%**** | 91.2 ± 7.2%**** | 60.3 ± 4.8%**** |
| Scriptaid (10 μM) | HDAC | 73.0 ± 10.9%**** | 69.7 ± 6.0%**** | 81.8 ± 2.1%**** |
| Nullscript (10 μM) | HDAC | 5.9 ± 7.2% | 10.9 ± 8.6% | 10.8 ± 12.5% |
| PI3K I VIII (250 nM) | PI3 kinase | 82.7 ± 6.4%**** | 81.7 ± 5.7%**** | 0% |
| Flt3 inhibitor (1 μM) | Flt3 | 76.1 ± 1.0%**** | 69.8 ± 1.3%**** | 88.7 ± 1.0%**** |
| Bisindolemal. (10 μM) | PKC | 16.1 ± 4.8% | 25.4 ± 5.0%*** | 28.4 ± 3%**** |
Potential oxytosis/ferroptosis inhibitors were tested for their ability to protect mouse HT22 hippocampal cells against glutamate, erastin and RSL3 toxicity at doses that induce 85%-95% cell death. Initially, a range of inhibitor concentrations were tested based on literature reports. The most effective concentrations are reported here. The values presented are the average of a minimum of five independent experiments with all treatments done in triplicate.
***
p<0.001;
****
p<0.0001 versus glutamate, erastin or RSL3 alone.