Table 2.
Inhibition of the choroidal glutathione S-transferase activity by environmental chemicals and therapeutic drugs
| Potential substrate | Potential substrate concentration (μm) | Reference substrate concentration CDNB (μm) | Origin of choroid plexus | Inhibition (%) |
|---|---|---|---|---|
| Ethacrynic acid | 5 | 200 | 4V | 91.7 ± 1.5 |
| LV | 81.2 ± 4.9 | |||
| Bromosulfophtalein | 40 | 200 | 4V | 72.0 ± 3.5 |
| LV | 73.3 ± 3.8 | |||
| Menadione | 80 | 200 | 4V | 41.2 ± 7.4 |
| LV | 50.0 ± 19.5 | |||
| MCB | 200 | 200 | 4V | 77.7 ± 1.5 |
| LV | 82.7 ± 2.1 | |||
| Chlorambucil | 200 | 200 | 4V | 83.5 ± 3.8 |
| LV | 84.6 ± 2.7 | |||
| Benzyl-isothiocyanate | 500 | 200 | 4V | 84.7 ± 3.2 |
| LV | 79.5 ± 6.7 | |||
| Sulforaphane | 200 | 50 | 4V | 26.7 ± 5.5 |
| LV | 19.5 ± 6.2 | |||
| Trans-4-phenyl- | 500 | 50 | 4V | 58.1 ± 7.0 |
| 3-buten-2-one | LV | 53.5 ± 6.9 | ||
| Acrolein | 500 | 50 | 4V | 53.4 ± 10.1 |
| LV | 48.4 ± 10.3 | |||
| Cisplatin | 500 | 50 | 4V | 41.5 ± 9.3 |
| LV | 27.7 ± 10.3 |
The potential substrates include diuretic, anticancer, or diagnostic drugs (ethacrynic acid, bromosulfophthalein, chlorambucil, cisplatin); dietary supplements and flavoring agents (menadione, trans-4-phenyl-3-buten-2-one); phytochemicals (benzyl-isothiocyanate, sulforaphane); or environmental pollutants (acrolein, also a product of lipid peroxidation). The competition was tested using the multispecific GST substrate CDNB as a reference substrate in both lateral ventricle and fourth ventricle choroid plexuses. Data, expressed as percentages of activity inhibition, are mean values ± SD (n = 3–4 from multiple CP pools). Owing to the limited choroidal material available per litter, they were generated for only one efficient competing concentration. The reference substrate concentration was typically 200 μm. When a low inhibition was observed, CDNB was tested at a lower concentration to increase the inhibitory action of the compound. The average specific activities measured in lateral ventricle choroid plexus tissue in the absence of inhibitors were 96 ± 22 and 54 ± 10 nmol/min/mg of proteins toward 200 and 50 μm CDNB, respectively. The same activities measured in fourth ventricle choroid plexus tissue were 87 ± 15 and 48 ± 10 nmol/min/mg of proteins (Data are the mean ± SD of three different batches).