The transport activity of P-glycoprotein upon a change of the redox balance in lymphocytes of patients with chronic B-lymphocytic leukemia

Abstract

The effect of drugs used in the treatment of chronic B-lymphocytic leukemia on the functional activity of P-glycoprotein, which is a membrane transporter associated with the phenomenon of multiple drug resistance, in B-lymphocytes of leukemia patients has been investigated. The level of reactive oxygen species and the content of low molecular weight antioxidants in the leukemic cells during the metabolic processing of chemotherapy drugs has been assessed. The degree of involvement of low molecular weight antioxidants in the maintenance of redox balance in the lymphocytes of drug-treated leukemia patients has been characterized. Variation of the levels of reactive oxygen species in leukemic B-lymphocytes within a certain range, as well as the subsequent return of these values to the levels of intact cells, was shown to enhance the P-glycoprotein transport activity. The viability of leukemic B-cells decreased upon exposure to antitumor compounds and depended on the redox balance. No statistically significant correlation between the P-glycoprotein transport activity and the viability of lymphocytes during the detoxification from drugs in B-cell chronic lymphocytic leukemia patients has been detected; however, the transport activity of the protein was directly correlated to the viability of leukemia cells within 15 h after exposure of the cells to H₂O₂.