Abnormal rheological response of erythrocytes caused by nitroimidazoles and hyperthermia

The aim of the present study was to investigate the response of erythrocytes to hyperthermia in combined treatment with nitroimidazoles. The efficiency of nitroimidazoles and physical agents on the rheological response of erythrocytes was measured by the viscosimetric-diffractometric method in a continuous osmotic gradient with constant shear stress of 100 dyn/cm2. We found that three newly synthesized dinitro- or nitroimidazole derivatives caused oxidative damage of erythrocytes in aerobic conditions. Nitroimidazole structure-dependent decrease of erythrocyte deformability was accompanied by oxidation of haemoglobin and depletion of reduced glutathione, lipid peroxidation and alteration of membrane structure indicated by a decrease of the ANS fluorescence intensity and increased production of MDA. Heat treatment per se (from 42 to 45 degrees C) only slightly decreased the erythrocyte deformability, but markedly enhanced the structure-dependent effect of nitroimidazoles. Erythrocytes heated at 45 degrees C with dinitroimidazole derivative III lost their deformability without haemolysis. Dithiothreitol used in combination with nitroimidazoles during a heating period to 43.5 degrees C protected cell deformability entirely, indicating an important role for disulphide bond formation in membrane proteins submitted to oxidative stress and hyperthermia.