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内容記述 |
Intestinal irradiation can cause both acute injuries related to epithelial cell damage and late injury related to vascular endothelial cell damage. p53 regulates the cellular response to radiation and functions as a radioresistant factor against both the injuries. We have identified several p53-regulating radioprotective compounds. Among them, sodium orthovanadate (vanadate), which has p53 inhibitory activity, is effective against radiation bone marrow damage in which p53 acts in a damage-promoting manner, but not against acute intestinal injury. However, in the present study, we found that vanadate is effective against delayed intestinal injury. The caudal half-body irradiation technique was utilized to induce delayed intestinal injury in C3H mice. With cranial half-body shielding using lead, the caudal half-body was irradiated with 6 Gy daily for 4 consecutive days. Vehicle (normal saline) or vanadate was injected intraperitoneally 30 minutes before each irradiation. In results, vanadate-treated mice survived the delayed intestinal death that occurred from 30 days of post irradiation. The results of the FITC-dextran permeability assay showed that the intestinal mucosal permeability of vanadate-administered mice was comparable to that of vehicle-treated mice, suggesting that vanadate has no protective effect on delayed injury by protecting the intestinal epithelium. An evaluation of this vanadate effect, focusing on delayed vascular endothelial damage, is currently under investigation. |
