Table 4:
6OHDA, PQ, CdCl2, cisplatin
| Compound | 6OHDA (500 μM) | PQ (2.5 mM) | CdCl2 (50 μM) | Cisplatin (100 μM) |
|---|---|---|---|---|
| No treatment | 14.2 ± 2.7% | 10.6 ± 5.3% | 6.7 ± 4.0% | 26.7 ± 5.0% |
| Ferrostatin (10 μM) | 18.8 ± 5.3% | 19.1 ± 4.0% | 11.6 ± 9.5% | 31.6 ± 5.2% |
| Liproxstatin (1 μM) | 20.0 ± 6.5% | 15.0 ± 5.1% | 11.7 ± 4.5% | 30.5 ± 3.7% |
| Deferiprone (100 μM) | 100 ± 5.0%**** | 14.5 ± 1.3% | 14.9 ± 10.0% | 31.4 ± 6.3% |
| MitoQ (1 μM) | 30.6 ± 6.7%* | 1.1 ± 1.6% | 0% | 60.7 ± 6.4%**** |
| Clorgyline (100 μM) | 22.7 ± 9.5% | 4.9 ± 3.9% | 6.1 ± 6.2% | 31.2 ± 13% |
| 968 (10 μM) | 22.3 ± 6.5% | 27.9 ± 8.5%*** | 2.1 ± 2.1% | 38.2 ± 4.4% |
| GSK2795039 (10 μM) | 10.5 ± 1.6% | 2.2 ± 2.4% | 15.2 ± 3.7% | 27.7 ± 6.1% |
| GKT137831 (10 μM) | 21.1 ± 6.4% | 7.0 ± 2.7% | 4.2 ± 1.4% | 21.7 ± 1.2% |
| PD146176 (5 μM) | 34.9 ± 10.3%** | 33.7 ± 8.2%**** | 6.8 ± 4.8% | 39.3 ± 6.6% |
| Troglitazone (1 μM) | 24.4 ± 6.4% | 16.1 ± 10.7% | 5.8 ± 0.8% | 33.6 ± 1.9% |
| Idebenone (1 μM) | 18.5 ± 7.3% | 3.4 ± 4.7% | 6.0 ± 3.1% | 26.3 ± 4.1% |
| CoCl2 (100 μM) | 44.0 ± 2.1%**** | 4.2 ± 4.2% | 0% | 33.1 ± 6.7% |
| LY83583 (1 μM) | 27.1 ± 7.9% | 5.0 ± 0.8% | 0% | 0%**** |
| Apomorphine (5 μM) | 24.4 ± 8.8% | 3.9 ± 4.3% | 0.8 ± 1.1% | 29.0 ± 2.4% |
| BI-6C9 (10 μM) | 29.8 ± 5.0% | 9.2 ± 1.7% | 8.2 ± 4.1% | 38.4 ± 5.2% |
| Bafilomycin (100 nM) | 26.1 ± 4.1% | 0.6 ± 0.06% | 4.0 ± 1.2% | 28.5 ± 4.7% |
| Scriptaid (10 μM) | 51.7 ± 2.6%**** | 0% | 5.7 ± 5.7% | 53.2 ± 9.5%*** |
| Nullscript (10 μM) | 21.4 ± 5.7% | 0% | 4.6 ± 4.1% | 41.6 ± 10% |
| Flt3 inhibitor (1 μM) | 15.5 ± 8.6% | 1.3 ± 1.8% | 12.3 ± 5.9% | 25.7 ± 6.6% |
The oxytosis/ferroptosis inhibitors that were effective against glutamate, erastin and RSL3 as shown in Table 1 were tested for their ability to protect mouse HT22 hippocampal cells against 6OHDA, PQ, CdCl2 and cisplatin at doses that induce 85%-95% cell death except for cisplatin where the maximum cell death never exceeded ~75%. The inhibitor concentrations that were most effective in the studies shown in Table 1 were used. The values presented are the average of a minimum of three independent experiments with all treatments done in triplicate.
*
p<0.05;
**
p<0.01;
***
p<0.001;
****
p<0.0001 versus 6OHDA, PQ, CdCl2 or cisplatin alone.