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

Abstract

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 γ-radiation doses (5–9 Gy) and full-thickness excision wound sizes (1–3 cm²) 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 cm² 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-β and FGF, and down-regulated PDGF-α, TNF-α, IL-1β, IL-6, MIP-1α, 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.

Keywords:

• Ascorbic acid
• chemokines
• radiation combined wound injury
• cytokines
• growth factors
• hematopoiesis
• immune system
• radiation dose

Acknowledgment

We are thankful to the Director, INMAS, for providing the resources to carry out the experiments and to Dr. B.G. Roy for providing the experimental animal facility for animal work in this study. The authors further thank Mr. Pradeep Goswami, the Radiation Safety Officer, for his assistance in setting up the radiation dosimeter and animal irradiation. The authors would also like to express their gratitude to Mr. Kennedy Roy, English teacher at Victoria Boys’ School in West Bengal, and Ms. Priyadarshini Moirangthem Chanu, lecturer of English at MECI Explorer Academy in Manipur, for their assistance in editing.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All the data are available.

Additional information

Funding

The research work was carried out in project no. TD/22-23/INM-327, Ministry of Defence, and the Government of India.

Notes on contributors

Ajay Kumar Sharma

Ajay Kumar Sharma, PhD, is working as a scientist at INMAS, DRDO, New Delhi. His research area includes the development of animal models for various types of combat emergencies (burn, wound, infection, diabetic, and combined radiation), and the development of appropriate countermeasures for such types of injuries.

Aman Kalonia

Aman Kalonia, M.Sc., is working as a research scholar at INMAS, DRDO, New Delhi. His research interests include the development of wound healing drugs for acute and complex wounds in combat causality management.

Rishav Kumar

Rishav Kumar, M.Sc., is working as a research scholar at INMAS, DRDO, New Delhi. His research area includes the development of animal models for combined radiation burn injuries and the in-depth study of pathophysiological and molecular changes during combined radiation injuries.

Kirti

Kirti, M.Sc., is working as a research scholar at INMAS, DRDO, New Delhi. Her research interests include the development of animal models for combined radiation injuries and the comprehensive examination of alterations in DNA damage marker levels that occur in the context of combined radiation injuries.

Priyanka Shaw

Priyanka Shaw, M.Sc., is working as a research scholar at INMAS, DRDO, New Delhi. Her research area includes the in-depth study of burn wounds and the development of burn wound healing drugs for combat causality management.

M. H. Yashvarddhan

M. H. Yashvarddhan, PhD, is working as a research scientist at INMAS, DRDO, New Delhi. His research interests include the development of animal models for radiation syndromes and countermeasures agents against radiation injuries.

Arpana Vibhuti

Arpana Vibhuti, PhD, is working as an associate professor and head of the Department of Biotechnology at SRM University, Sonepat, Haryana. Her research interests include the investigation of telomeres and telomerase-associated biomarkers in the pathogenesis of oxidative stress-associated diseases, including high-altitude disorders, cancer, and COVID-19.

Sandeep Kumar Shukla

Sandeep Kumar Shukla, PhD, is working as a senior scientist at INMAS, DRDO, New Delhi. His research area includes the development of animal models for various types of combat emergencies (burn, wound, infection, diabetic, radiation, and combined radiation), the development of countermeasures for radiological and nuclear emergencies, toxicology, and drug development for combat causality management.