Morphological Transformation and Phosphatidylserine Exposure in Erythrocytes Treated with Ribavirin

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The effects of intracellular ribavirin on morphology and redistribution of phosphatidylserine (PS) in human erythrocytes were examined. Erythrocytes were incubated with 1 mM ribavirin in the presence/absence of dipyridamole, an inhibitor of es-type nucleoside transporter. Intracellular ribavirin was accumulated in erythrocytes with the concentration of 1361 μM, which corresponds to the blood level in patients receiving ribavirin. Dipyridamole reduced ribavirin accumulation by 40.7% (807 μM) via inhibiting es-type nucleoside transporter on erythrocytes. Morphological transformation into echinocytic form was observed in 86.4% of the erythrocytes treated with ribavirin. Dipyridamole pre-treatment decreased the morphological change to 20.0%. Ribavirin increased the PS-exposing cells compared with control (2.15% vs. 0.87%). PS-exposing cells were also decreased by inhibiting ribavirin accumulation with dipyridamole (0.62%). The results suggest that intracellular ribavirin induces morphological change and PS exposure in erythrocytes and accelerates erythrophagocytosis in the reticuloendothelial system.