Mn porphyrins reduce eryptosis, SSRBC oxidative stress, and leukocytosis in TS mice in vivo. TS mice were dosed daily for 28 days except on weekends with 1 dose per day of vehicle, 0.1 mg/kg MnBuOE, and 1 mg/kg MnE injected subcutaneously. (A) PS exposure of sickle RBCs in treated TS mice. Dynamics of RBC PS exposure analyzed with GFP-labeled annexin V on Mn porphyrin-improved eryptosis in TS mice. The data presented as SEM of 5 different experiments per treatment group. ***P < .001 vs vehicle. (B) SSRBC ROS production in treated TS mice. SSRBCs isolated from blood of treated TS mice were tested for the levels of ROS using DCF as an indicator of ROS in cells. MnBuOE and MnE significantly decreased ROS production in sickle RBCs compared with vehicle treatment. Error bars show SEM of 6 different experiments per treatment group. ****P < .0001 vs vehicle. (C-F) Leukocytosis evaluation in treated sickle mice. Blood drawn through the submandibular vein was assessed for complete blood count. Total leukocyte (C), neutrophil (D), lymphocyte (E), and monocyte (F) counts are shown. Data are presented as SEM. *P < .05 and **P < .01 compared with vehicle controls.