Hesperidin enhances the repair and regeneration of full-thickness dermal wounds in mice exposed to fractionated γ-radiation

Background and aim: Neoplasms are often clinically treated with radiation therapy, which is known for its therapeutic benefits. However, pre-surgical radiotherapy is associated with a high incidence of surgical wound healing complications, necessitating the exploration of new pharmacological approaches. This study investigates the effects of 100 mg/kg oral hesperidin on mice undergoing hemi-body irradiation with varying fractionated γ-radiation doses. Methods: Mice were exposed to 10, 20, or 40 Gy doses of fractionated γ-radiation (2 Gy/day) below the rib cage. Full-thickness excision wounds were created on their dorsum, and wound contractions were assessed periodically through video imaging. Biochemical profiles were analyzed by measuring collagen content, DNA synthesis, and nitric oxide (NO) levels in granulation tissue, as well as glutathione (GSH) levels, GSH peroxidase (GSHpx) activity, and lipid peroxidation (LPx) in the skin. Histological examinations were conducted at various post-irradiation intervals to assess skin regeneration. Results: Fractionated irradiation delayed wound contraction and prolonged mean wound healing time (MHT) in a dose-dependent manner, reducing collagen content, DNA synthesis, and NO levels in granulation tissue. In addition, irradiation decreased GSH concentrations and GSHpx activity while increasing LPx, with severity correlating to radiation dose. Fibroblast and vascular densities also declined following fractionated irradiation. In contrast, pre-treatment with hesperidin significantly enhanced wound contraction, reduced MHT, and increased collagen levels, DNA synthesis, and NO production. Furthermore, hesperidin treatment elevated GSH levels and GSHpx activity while decreasing radiation-induced LPx. In addition, hesperidin pre-treatment improved collagen deposition and fibroblast and vascular densities. Conclusion: This study demonstrates that hesperidin accelerates wound healing after fractionated radiation, suggesting hesperidin’s potential as a therapeutic paradigm in managing irradiated wounds. Relevance for patients: The use of hesperidin is expected to mitigate the complications of surgical wounds arising after radiotherapy of cancer patients in a clinical setting.