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Results: 5

1.
Figure 1

Figure 1. Effect of captopril on drinking water consumption. From: Timing of captopril administration determines radiation protection or radiation sensitization in a murine model of total body irradiation.

Volume of water consumed was measured each day for the full time course of the experiment. The estimated volume of water consumed per mouse was calculated. Captopril was administered pre-irradiation from day −7 to day 0 (day of irradiation). Captopril administered postirradiation was from day 0 (beginning 1 hour after irradiation) to day +30.

Thomas A. Davis, et al. Exp Hematol. ;38(4):270-281.
2.
Figure 2

Figure 2. Treatment of mice with captopril following high-dose irradiation is radioprotective whereas treatment prior to irradiation has a radiosensitization effect. From: Timing of captopril administration determines radiation protection or radiation sensitization in a murine model of total body irradiation.

Mice were untreated or were administered captopril (0.1 mg/kg/day) in their drinking water before and/or after exposure to 7.5 Gy 60Co gamma total body irradiation (TBI). (A) The percentage of mice surviving at 30 days is shown. Results represent a total of 16-20 mice per group. * p < 0.05 from untreated irradiated mice. ** p < 0.001 from untreated irradiated mice. (B) Graph of 30 day survival. (C) Time-dependent change in body weight in nonirradiated control mice or mice that received captopril in their drinking water before and/or after exposure to 7.5 Gy 60Co TBI. Data represent the change in body weight ± standard error (SEM). n = 20 mice per group). Statistical findings are noted in the text.

Thomas A. Davis, et al. Exp Hematol. ;38(4):270-281.
3.
Figure 5

Figure 5. Captopril administration to nonirradiated control mice transiently dampens HPC bone marrow progenitor entry into the cell cycle (day 2) followed by a modest increase into G1 to G2 transition (day 7). From: Timing of captopril administration determines radiation protection or radiation sensitization in a murine model of total body irradiation.

Mice were either untreated (control), or treated with captopril (0.1 mg/kg/day) for 2 or 7 days. Femoral bone marrow was obtained and Lin- cells were isolated from pooled femoral bone marrow cells by MACS selection. Cells were stained for Sca-1 and c-Kit cell surface expression. The cell cycle was determined by Ki67-FITC and 7AAD staining using multicolor flow cytometry. Data shown are the mean ± SEM of three separate experiments using pooled marrow from two mice per group, *p < 0.05 from control. (Panel A) Lin cells (HPC enriched cells). (Panel B) Lin Sca-1+cKit+ (LSK+, HSC enriched cells).

Thomas A. Davis, et al. Exp Hematol. ;38(4):270-281.
4.
Figure 4

Figure 4. Effect of captopril on nucleated cell bone marrow reconstitution in irradiated mice. From: Timing of captopril administration determines radiation protection or radiation sensitization in a murine model of total body irradiation.

Mice were 1) untreated irradiated, 6.0 Gy total body irradiation (TBI-control group), 2) pretreated with captopril (0.1 mg/kg/day) for 7 consecutive days before irradiation, or 3) irradiated and then given captopril (0.1 mg/kg/day) for 14 consecutive days. At days 5 and 14 postirradiation, femoral bone marrow cells were collected. (Panel A) Total number of nucleated leukocytes cells per femur postirradiation. The number of assayable multilineage and lineage specific colony-forming progenitor cells were determined from bone marrow cells collected at day 5 (Panel B) and day 14 (Panel C) postirradiation. Multipotential (CFU-GEMM), myeloid (CFU-GM, CFU-M), and erythroid (BFU-E) bone marrow colony forming cells were determined. For all panels, results represent means ± SEM of six mice. * p < 0.05, compared with TBI-treated group; † p < 0.05 compared with the captopril pretreatment-treated group. For comparison purposes the bone marrow cellularity of untreated nonirradiated mice was 20.37 × 106 nucleated leukocytes/femur (data not shown).

Thomas A. Davis, et al. Exp Hematol. ;38(4):270-281.
5.

Figure 3. Effect of captopril administration on radioprotection. From: Timing of captopril administration determines radiation protection or radiation sensitization in a murine model of total body irradiation.

Mice received no treatment or were administered captopril in their drinking water before (day −7 to day 0= day of irradiation) or after (day 0 [starting 1 hour after irradiation] to day 30) exposure to 7.5 Gy 60Co gamma total body irradiation. (Panel A) Peripheral blood white blood cells (WBC), red blood cells (RBC), reticulocytes, lymphocytes, platelets, and absolute neutrophils from irradiated mice, samples were taken at 2 hours (indicated on day 0), 2 7 10 or 14 days postirradiation. Control blood cell levels in untreated, nonirradiated mice are also indicated for blood cell types, except for lymphocytes (3.84 × 103 ± 0.4) and WBC (4.4 × 103 ± 0.5). Data show mean values ± SEM, n = 5-6 mice per group. * p < 0.05 compared with radiation alone cell counts at the same time point. (Panel B) Histological comparison of brain microhemorrhages in the subcortical cerebrum (100 × magnification) and cerebellar cortex (200 × magnification) of mice at day 14 postirradiation. Representative photomicrographs of hematoxylin and eosin stained tissue for mice treated with captopril prior to (upper panels with hemorrhage) or following (lower panels, normal brain) radiation exposure. The microhemorrhages are indicated by arrows and occur periventricularly in the subcortical cerebrum; ventricles (V) and corpus callosum (CC) are identified for orientation. Microhemorrhages also occured perivascularly in the cerebellar cortex extending from the white matter (WM) through the granular (G) and piriform/Purkinje (P) layers, abutting the molecular (M) layer.

Thomas A. Davis, et al. Exp Hematol. ;38(4):270-281.

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