Inhibition of erythrocyte glutathione conjugate transport by polyethoxylated surfactants.

The surfactant Cremophor EL has recently been shown to reverse the multiple drug resistance phenotype (mdr1) created by over-expression of P glycoprotein, an ATP dependent membrane transport system. Oxidize glutathione and glutathione thioethers are transported out of cells by ATP dependent systems that are distinct from the P glycoprotein pathway. The present study shows that Cremophor EL and a number of other polyethoxylated surfactants inhibit the transport of 2,4-dinitrophenyl glutathione out of intact erythrocytes. The inhibition is not complete, suggesting that this inhibition may differentiate between different glutathione transporters. ATP concentrations are maintained within the cells incubated with Cremophor EL indicating that the inhibition is not mediated by metabolic deprivation.