Figure 4
Figure 4. Effects of RAP-536 on hemolysis, RBC morphology, Heinz bodies, and α-globin chain distribution in Hbbth1/th1 mice. Hbbth1/th1 mice (3-4 months old) were treated with RAP-536 or vehicle as in Figure 2, and age-matched wild-type mice treated with vehicle were used as additional controls. (A) Total bilirubin concentration (n = 10-13 mice per group). (B) Blood smears treated with Wright-Giemsa stain to reveal effects of RAP-536 on RBC morphology, reticulocyte number, cellular debris, and degree of poikilocytosis. (C) Representative high-performance liquid chromatogram showing reduction of α-globin aggregates in erythrocyte membranes from Hbbth1/th1 mice treated with RAP-536. Mean levels of α-globin aggregates were reduced 38% by RAP-536 treatment. n = 3 to 5 mice per group. (D) Blood cells stained supravitally with new methylene blue and counterstained with Wright-Giemsa to reveal Heinz bodies. Images in B and D were obtained with a 100× oil immersion objective; bar = 10 µm. Data are means ± SEM. ###P < .001 vs wild type; **P < .01, RAP-536 vs vehicle.

Effects of RAP-536 on hemolysis, RBC morphology, Heinz bodies, and α-globin chain distribution in Hbbth1/th1 mice.Hbbth1/th1 mice (3-4 months old) were treated with RAP-536 or vehicle as in Figure 2, and age-matched wild-type mice treated with vehicle were used as additional controls. (A) Total bilirubin concentration (n = 10-13 mice per group). (B) Blood smears treated with Wright-Giemsa stain to reveal effects of RAP-536 on RBC morphology, reticulocyte number, cellular debris, and degree of poikilocytosis. (C) Representative high-performance liquid chromatogram showing reduction of α-globin aggregates in erythrocyte membranes from Hbbth1/th1 mice treated with RAP-536. Mean levels of α-globin aggregates were reduced 38% by RAP-536 treatment. n = 3 to 5 mice per group. (D) Blood cells stained supravitally with new methylene blue and counterstained with Wright-Giemsa to reveal Heinz bodies. Images in B and D were obtained with a 100× oil immersion objective; bar = 10 µm. Data are means ± SEM. ###P < .001 vs wild type; **P < .01, RAP-536 vs vehicle.

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