Radioprotector WR-2721 and mitigating peptidoglycan synergistically promote mouse survival through the amelioration of intestinal and bone marrow damage.
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.
Affiliation: School of Radiation Medicine and Protection, Soochow University, No. 199 Ren'ai Road, Suzhou 215123, PR China.Show MeSH
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Mentions: Histological changes in the ilea were characterized by the adherence of submucosal layers and sloughing of crypts, as well as ulcers and ruptured villi in 10 Gy irradiated mice (Fig. 3). Irradiated animals that received either WR-2721 or PGN evidently had longer villi and more crypts compared with untreated irradiated mice four days after 10 Gy IR (Fig. 3). Furthermore, irradiated mice treated with a combination of PGN and WR2721 had normal mucosal thickness, minimal inflammatory changes, and preserved tissue architecture.Fig. 3.
Affiliation: School of Radiation Medicine and Protection, Soochow University, No. 199 Ren'ai Road, Suzhou 215123, PR China.