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Radioprotector WR-2721 and mitigating peptidoglycan synergistically promote mouse survival through the amelioration of intestinal and bone marrow damage.

Liu W, Chen Q, Wu S, Xia X, Wu A, Cui F, Gu YP, Zhang X, Cao J - J. Radiat. Res. (2015)

Bottom Line: Furthermore, combined PGN and WR-2721 treatment had an obviously synergistic radio-protective effect in nucleated cells in the bone marrow, including GEMM progenitors and CD45(+)CD34(+) cells 4 days after 10 Gy IR.The NF-κB p65 subunit was translocated to the nucleus, and phosphate-IκBα (Ser32/Ser36) was detected after stimulation with either PGN or WR-2721, which indicates that these two agents act synergistically through the activation of the NF-κB pathway.Administration of PGN in combination with WR-2721 was demonstrated to have a synergistic effect on the increase in haematopoietic cells and intestinal reconstitution, as well as improved survival in lethally irradiated mice, but resulted in some degree of an immune disorder.

View Article: PubMed Central - PubMed

Affiliation: School of Radiation Medicine and Protection, Soochow University, No. 199 Ren'ai Road, Suzhou 215123, PR China.

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Related in: MedlinePlus

WR-2721 and PGN promoted recovery of intestinal absorption in irradiated mice. Xylose uptake assay of 10 mice per group was performed 1 day before mice were euthanized. Samples of urine were collected, and xylose levels were measured using a modified micro-method and normalized to data from unirradiated mice at the same time-points. On Day 3 after 10 Gy IR, the absorption rate of mice treated with WR-2721 + PGN demonstrated a clear difference from that of mice exposed to 10 Gy irradiation (P < 0.01). On Day 7, the absorption rate of mice treated with WR-2721 or PGN alone, or with WR-2721 + PGN, was obviously higher than that of the 10 Gy irradiated mice. Error bars indicate the SD for n = 10 mice (*P < 0.05).
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RRU100F4: WR-2721 and PGN promoted recovery of intestinal absorption in irradiated mice. Xylose uptake assay of 10 mice per group was performed 1 day before mice were euthanized. Samples of urine were collected, and xylose levels were measured using a modified micro-method and normalized to data from unirradiated mice at the same time-points. On Day 3 after 10 Gy IR, the absorption rate of mice treated with WR-2721 + PGN demonstrated a clear difference from that of mice exposed to 10 Gy irradiation (P < 0.01). On Day 7, the absorption rate of mice treated with WR-2721 or PGN alone, or with WR-2721 + PGN, was obviously higher than that of the 10 Gy irradiated mice. Error bars indicate the SD for n = 10 mice (*P < 0.05).

Mentions: As xylose is not metabolised in the body, the d-xylose absorption test is used to measure the level of d-xylose in blood or urine samples to help diagnose problems that prevent the small intestine from absorbing nutrients in food. In this study, urine xylose levels were tested 2 h after a test feeding dose at 3, 7, 15 and 35 days after 10 Gy IR. Normal unirradiated mice demonstrated 100% xylose absorption. As expected, a progressive reduction in xylose absorption rates was observed in irradiated mice. However, intestinal absorptive function was elevated in the combined treatment group compared with the IR group (Fig. 4), indicating that the combination of WR-2721 and PGN best restituted the intestinal villi damaged by IR compared with WR-2721 or PGN treatment alone.Fig. 4.


Radioprotector WR-2721 and mitigating peptidoglycan synergistically promote mouse survival through the amelioration of intestinal and bone marrow damage.

Liu W, Chen Q, Wu S, Xia X, Wu A, Cui F, Gu YP, Zhang X, Cao J - J. Radiat. Res. (2015)

WR-2721 and PGN promoted recovery of intestinal absorption in irradiated mice. Xylose uptake assay of 10 mice per group was performed 1 day before mice were euthanized. Samples of urine were collected, and xylose levels were measured using a modified micro-method and normalized to data from unirradiated mice at the same time-points. On Day 3 after 10 Gy IR, the absorption rate of mice treated with WR-2721 + PGN demonstrated a clear difference from that of mice exposed to 10 Gy irradiation (P < 0.01). On Day 7, the absorption rate of mice treated with WR-2721 or PGN alone, or with WR-2721 + PGN, was obviously higher than that of the 10 Gy irradiated mice. Error bars indicate the SD for n = 10 mice (*P < 0.05).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4380048&req=5

RRU100F4: WR-2721 and PGN promoted recovery of intestinal absorption in irradiated mice. Xylose uptake assay of 10 mice per group was performed 1 day before mice were euthanized. Samples of urine were collected, and xylose levels were measured using a modified micro-method and normalized to data from unirradiated mice at the same time-points. On Day 3 after 10 Gy IR, the absorption rate of mice treated with WR-2721 + PGN demonstrated a clear difference from that of mice exposed to 10 Gy irradiation (P < 0.01). On Day 7, the absorption rate of mice treated with WR-2721 or PGN alone, or with WR-2721 + PGN, was obviously higher than that of the 10 Gy irradiated mice. Error bars indicate the SD for n = 10 mice (*P < 0.05).
Mentions: As xylose is not metabolised in the body, the d-xylose absorption test is used to measure the level of d-xylose in blood or urine samples to help diagnose problems that prevent the small intestine from absorbing nutrients in food. In this study, urine xylose levels were tested 2 h after a test feeding dose at 3, 7, 15 and 35 days after 10 Gy IR. Normal unirradiated mice demonstrated 100% xylose absorption. As expected, a progressive reduction in xylose absorption rates was observed in irradiated mice. However, intestinal absorptive function was elevated in the combined treatment group compared with the IR group (Fig. 4), indicating that the combination of WR-2721 and PGN best restituted the intestinal villi damaged by IR compared with WR-2721 or PGN treatment alone.Fig. 4.

Bottom Line: Furthermore, combined PGN and WR-2721 treatment had an obviously synergistic radio-protective effect in nucleated cells in the bone marrow, including GEMM progenitors and CD45(+)CD34(+) cells 4 days after 10 Gy IR.The NF-κB p65 subunit was translocated to the nucleus, and phosphate-IκBα (Ser32/Ser36) was detected after stimulation with either PGN or WR-2721, which indicates that these two agents act synergistically through the activation of the NF-κB pathway.Administration of PGN in combination with WR-2721 was demonstrated to have a synergistic effect on the increase in haematopoietic cells and intestinal reconstitution, as well as improved survival in lethally irradiated mice, but resulted in some degree of an immune disorder.

View Article: PubMed Central - PubMed

Affiliation: School of Radiation Medicine and Protection, Soochow University, No. 199 Ren'ai Road, Suzhou 215123, PR China.

Show MeSH
Related in: MedlinePlus