Pre-irradiation administration of nilestriol promotes hematopoietic recovery but increases early mortality risk and impairs wound healing after total-body irradiation combined with wound trauma.

Abstract

Purpose: Estrogens are frequently employed as radioprotective agents in nuclear emergencies, yet their effects on radiation combined injury (RCI) are poorly understood. This study evaluated the impact of nilestiol on radiation-wound combined injury (R-W-CI).

Materials and methods: Mouse models included 6.0 and 8.0 Gy total body irradiation (TBI), 2.0% of the total body surface area (TBSA) skin wound trauma, and R-W-CI (6.0 or 8.0 Gy TBI followed by a 2% TBSA wound). Nilestriol was administered 3 and 1 day pre-injury. The outcomes assessed included 30-day survival, weight changes, peripheral blood analysis, wound closure, bone marrow-derived clonogenic activity, flow cytometric analysis of hematopoietic stem and progenitor cells, and splenic extramedullary hematopoiesis.

Results: Nilestriol significantly improved 30-day survival rate in mice subjected to 8.0 Gy TBI and enhanced hematopoietic recovery in those exposed to 6.0 Gy TBI. In wound-only models, nilestriol suppressed early inflammatory cytokines and impaired wound closure. For R-W-CI model with 8.0 Gy, nilestriol significantly improved the 30-day survival rate but increased the risk of early mortality. For R-W-CI with 6.0 Gy, nilestriol significantly promoted hematopoietic recovery, but led to a significant delay in wound healing by more pronounced inhibitory effects on the early inflammatory response in wounds of R-W-CI. No gender differences were observed in the effects of nilestriol. Additionally, Splenic extramedullary hematopoiesis was inhibited in nilestriol pretreatment groups.

Conclusion: These findings suggest that pre-irradiation administration of nilestriol can mitigate R-W-CI effects but requires careful consideration due to potential negative impacts on both systemic and local levels.