Peroxides inhibit the glutathione S-conjugate pump

Tert-Butyl hydroperoxide (100-300 microM) was found to inhibit the active efflux of dinitrophenyl-S-glutathione (DNP-SG) from human erythrocytes. From among amino acid peroxides generated by irradiation of amino acid (proline, valine and leucine) solutions, valine hydroperoxide (150 microM) had a similar effect on the DNP-SG transport. As the transport of glutathione S-conjugates is an important step of cellular detoxication, these results indicate that oxidative stress may impair cellular resistance to chemical stress of other kinds. t-Butyl and amino acid peroxides upon interaction with hemoglobin and whole erythrocytes produce free radicals which may be responsible for the damage to the glutathione S-conjugate pump of the erythrocyte membrane.