In vitro: In contrast to SK-N-BE(2) cells, co-treatment of IMR-32 cells with TTFA not only failed to stimulate formation of ROS produced by cisplatin, but rather suppressed it. This correlates with the attenuation of the caspase-3-like activity in response to combined treatment of IMR-32 cells with TTFA and cisplatin.
In vivo: TTFA-mediated inhibition of the ubiquinone-binding site of SDHD blocks electron transfer to ubiquinone and may lead to electron-slippage with the formation of superoxide radicals, thereby contributing to ROS production.
| Cell Experiment | |
|---|---|
| Cell lines | NB cell lines |
| Preparation method | For the time lapse, cells were cultivated in the POC-R cell cultivation system at 37 °C and a humidified air/CO2 (5%) atmosphere. Cisplatin ± TTFA was bath-applied before the start of the time lapse and the fluorescence was recorded for 22 h. |
| Concentrations | 75 μM, 100 μM |
| Incubation time | 24 h |
| Animal Experiment | |
|---|---|
| Animal models | |
| Formulation | |
| Dosages | |
| Administration | |
| Molecular Weight | 222.18 |
| Formula | C8H5F3O2S |
| CAS Number | 326-91-0 |
| Solubility (25°C) | 10 mM in DMSO |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
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