PEROXIDES INHIBIT THE GLUTATHIONE S-CONJUGATE PUMP

Tert-Butyl hydroperoxide (100-300 mu M) was found to inhibit the activ e efflux of dinitrophenyl-S-glutathione (DNP-SG) from human erythrocyt es. From among amino acid peroxides generated by irradiation of amino acid (proline, valine and leucine) solutions, valine hydroperoxide (15 0 mu M) had a similar effect on the DNP-SG transport. As the transport of glutathione S-conjugates is an important step of cellular detoxica tion, 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 prod uce free radicals which may be responsible for the damage to the gluta thione S-conjugate pump of the erythrocyte membrane.