Radioprotective and radiomitigative effects of BP-C2, a novel lignin-derived polyphenolic composition with ammonium molybdate, in two mouse strains exposed to total body irradiation

Figures & data

Table 1. Effect of BP-C2 on the outcome of acute radiation injuries in CBA mice.

	Survival (%) when exposed to dose (Gy)
Group	4.0	5.0	6.0	7.0	8.0
Placebo	91.7	75.0	50.0	0.0	0.0
BP-C2 (6.0 mg/kg)	100.0	83.3	41.7	4.2	0.0
BP-C2 (81.0 mg/kg)	100.0	91.7	75.0*	4.2	0.0
BP-C2 (156.2 mg/kg)	100.0	83.3	58.3	8.3	0.0

* Difference from placebo group is significant (p ≤ .05). n = 12 animals per group; data for 6.0 Gy and 7.0 Gy were pooled from 2 sets of experiments (n = 24 animals per pooled group).

Figure 1. Effect of BP-C2 on survival of CBA mice after TBI. BP-C2 or Placebo were given by gavage 5 times every second day prior to, and 5 times every second day after, irradiation. n = 12 animals per group at 5.0 Gy and n = 24 animals per pooled group at 6.0 and 7.0 Gy from two sets of experiments.

Table 2. Effect of BP-C2 on LD₅₀ doses in CBA mice.

		Lethal dose (Gy, M ± m, in parentheses – CI)
Experimental group	Drug dose (mg/kg)	LD16/30	LD50/30	LD84/30
Placebo	—	4.6	5.7 ± 0.2 (5.3–6.1)	6.8
BP-C2	6.0	4.9	5.8 ± 0.2 (5.4–6.2)	6.2
BP-C2	81.0	5.4	6.2 ± 0.2 (5.8–6.6)	7.1
BP-C2	156.2	5.1	6.0 ± 0.2 (5.7–6.3)	6.9

Figure 2. Effect of BP-C2 on weight of spleen and number of CFUs in CBA mice on day 10 after TBI. BP-C2 (81 mg/kg) was given by gavage 5 times every second day prior to, and 5 times every second day after, 5.7 Gy irradiation. (a) Weight of spleen. (b) CFUs. Data are presented as M ± SD. ****p < .0001. n = 12 animals per group.

Table 3. Effect of BP-C2 on the survival of C57BL/6 mice on day 8 after total body irradiation.

Radiation dose (Gy)	Experimental group	Survival (%)	Mean survival time (day, M ± m)
5.0	Placebo	100	>8.0
	BP-C2	100	>8.0
6.0	Placebo	60	7.2 ± 0.4
	BP-C2	50	6.6 ± 0.5
7.0	Placebo	10	5.5 ± 0.4
	BP-C2	50*	7.0 ± 0.4*
8.0	Placebo	0	4.4 ± 0.3
	BP-C2	10	5.2 ± 0.6

* Difference from respective placebo group is statistically significant (p < .05). n = 10 in each group.

Figure 3. Effect of BP-C2 on nucleated bone marrow cell count in C57BL/6 mice on day 8 after TBI. BP-C2 (81 mg/kg) was given by gavage daily 7 times starting 24 h after irradiation. Data are presented as M ± SD. ****p < .0001 versus control.

Figure 4. Survival curves for nucleated bone marrow cells. Effect of therapeutic administration of BP-C2 on survival of nucleated bone marrow cells in C57BL/6 mice on day 8 after irradiation. (a) Placebo groups, (b) BP-C2 (81 mg/kg) groups. D_q – quasi-threshold dose representing the cells’ self-repair capacity, n – extrapolation coefficient.

Figure 5. Effect of BP-C2 on weight of spleen and number of CFUs in C57BL/6 mice on day 8 after TBI. BP-C2 (81 mg/kg) was given by gavage daily 7 times starting 24 hours after irradiation. (a) Weight of spleen. (b) CFUs. Data are presented as M ± SD. Control group – 0.0 Gy n = 10; placebo groups – 5.0 Gy n = 10, 6.0 Gy n = 6; BP-C2 groups – 5.0 Gy n = 10, 6.0 Gy n = 5. CFUs: spleen colony-forming units; TBI: total body irradiation; n: number of animals. ****p < .0001 versus control. ***p = .0002 versus Control. #p = .0245 versus placebo 5.0 Gy.

Figure 6. Effect of BP-C2 on number of SIC in C57BL/6 mice on day 8 after TBI. BP-C2 (81 mg/kg) was given by gavage daily starting 24 h after irradiation 7 times. Data are presented as M ± SD. Control group – 0.0 Gy n = 10 (100), placebo groups – 5.0 Gy n = 10 (90), 6.0 Gy n = 6 (60), 7.0 Gy n = 1 (10), BP-C2 groups – 5.0 Gy n = 10 (83), 6.0 Gy n = 5 (48), 7.0 Gy n = 5 (46), 8.0 Gy n = 1 (10). n – number of animals (number of intestinal cross-sections scored). ***, ****p < .001, p < .0001 versus Control. ##p = .0023 BP-C2 5.0 Gy versus placebo 5.0 Gy, ####p < .0001 BP-C2 6.0 Gy versus. placebo 6.0 Gy.

Figure 7. Effect of BP-C2 on Lgr5 + cells of intestinal crypts in C57BL/6 mice on day 8 after TBI. (a) Control 0.0 Gy; (b) Placebo 5.0 Gy; (c) BP-C2 (81 mg/kg) 5.0 Gy; (d) Placebo 7.0 Gy (note marked loss of intestinal crypts along with depletion of Lgr5 + cells); (e) BP-C2 (81 mg/kg) 7.0 Gy; (f) Number of Lgr5 + cells of intestinal crypts (data are presented as M ± SEM). **p < .01, ****p < .0001 versus Control, ###p < .001, ####p < .0001 BP-C2 group versus placebo group. Scale bar – 500 μm.

Figure 8. PCNA + cells of intestinal crypts in C57BL/6 mice on day 8 after TBI. BP-C2 (81 mg/kg) was given by gavage daily 7 times starting 24 hours after irradiation. Data are presented as M ± SD.