Alleviation of radiation combined skin injury in rat model by topical application of ascorbate formulation

Purpose This research endeavor was undertaken to elucidate the impact of an innovative ascorbate formulation on the regeneration process of full-thickness excision wounds in a rat model exposed to whole-body gamma irradiation, replicating conditions akin to combat or radiation emergency scenarios. Materials and Methods We established a comprehensive rat model by optimizing whole body gamma-radiation doses (5-9 Gy) and full-thickness excision wound sizes (1-3 cm(2)) to mimic radiation combined injury (RCI). The developed RCI model was used to explore the healing potential of ascorbate formulation. The study includes various treatment groups (i.e., sham control, radiation alone, wound alone, radiation + wound, and radiation + wound + formulation). The ascorbate formulation was applied twice daily, with a 12-hour gap between each application, starting 1 hour after the initiation of the wound. The healing potential of the formulation in the RCI context was evaluated over 14 days through hematological, molecular, and histological parameters. Results The combination of a 5 Gy radiation dose and a 1 cm(2) wound was identified as the optimal setting to develop the RCI model for subsequent studies. The formulation was used topically immediately following RCI, and then twice daily until complete healing. Treatment with the ascorbate formulation yielded noteworthy outcomes and led to a substantial reduction (p < .05) in the wound area, accelerated epithelialization periods, and an increased wound contraction rate. The formulation's localized healing response improved organ weights, normalized blood parameters, and enhanced hematopoietic and immune systems. A gene expression study revealed the treatment up-regulated TGF-beta and FGF, and down-regulated PDGF-alpha, TNF-alpha, IL-1 beta, IL-6, MIP-1 alpha, and MCP-1 (p < .05). Histopathological assessments supported the formulation's effectiveness in restoring cellular architecture and promoting tissue regeneration. Conclusion Topical application of the ascorbate formulation in RCI resulted in a significant improvement in delayed wound healing, leading to accelerated wound closure by mitigating the expression of inflammatory responses.