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Journal of Clinical and

                                                                  Translational Research



                                        ORIGINAL ARTICLE
                                        Hesperidin enhances the repair and

                                        regeneration of full-thickness dermal wounds in
                                        mice exposed to fractionated γ-radiation



                                        Ganesh Chandra Jagetia*  and Kota V. N. M. Rao

                                        Department of Zoology, School of Life Sciences, Mizoram University, Aizawl, Mizoram, India
                                        (This article belongs to the Special Issue: Innovations in wound healing)




                                        Abstract

                                        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
            *Corresponding author:      hemi-body irradiation with varying fractionated γ-radiation doses. Methods: Mice
            Ganesh Chandra Jagetia
            (gc.jagetia@gmail.com)      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,
            Citation: Jagetia GC, Rao KVNM.
            Hesperidin enhances the repair   and wound contractions were assessed periodically through video imaging.
            and regeneration of full-thickness   Biochemical profiles were analyzed by measuring collagen content, DNA synthesis,
            dermal wounds in mice exposed   and nitric oxide (NO) levels in granulation tissue, as well as glutathione (GSH)
            to fractionated γ-radiation. J Clin
            Transl Res. 2025;11(1):34-55.   levels, GSH peroxidase (GSHpx) activity, and lipid peroxidation (LPx) in the skin.
            doi: 10.36922/jctr.24.00049  Histological examinations were conducted at various post-irradiation intervals
            Received: July 31, 2024     to assess skin regeneration.  Results: Fractionated irradiation delayed wound
                                        contraction and prolonged mean wound healing time (MHT) in a dose-dependent
            1st revised: November 13, 2024
                                        manner, reducing collagen content, DNA synthesis, and NO levels in granulation
            2nd revised: November 20, 2024  tissue. In addition, irradiation decreased GSH concentrations and GSHpx activity
            Accepted: January 17, 2025  while increasing LPx, with severity correlating to radiation dose. Fibroblast and
                                        vascular densities also declined following fractionated irradiation. In contrast,
            Published online: February 7,
            2025                        pre-treatment with hesperidin significantly enhanced wound contraction,
                                        reduced MHT, and increased collagen levels, DNA synthesis, and NO production.
            Copyright: © 2025 Author(s).
            This is an open-access article   Furthermore, hesperidin treatment elevated GSH levels and GSHpx activity while
            distributed under the terms of the   decreasing radiation-induced LPx. In addition, hesperidin pre-treatment improved
            Creative Commons AttributionNon-  collagen deposition and fibroblast and vascular densities. Conclusion: This study
            Commercial 4.0 International (CC
            BY-NC 4.0), which permits all   demonstrates that hesperidin accelerates wound healing after fractionated
            non-commercial use, distribution,   radiation, suggesting hesperidin’s potential as a therapeutic paradigm in managing
            and reproduction in any medium,   irradiated wounds. Relevance for patients: The use of hesperidin is expected to
            provided the original work is
            properly cited.             mitigate the complications of surgical wounds arising after radiotherapy of cancer
                                        patients in a clinical setting.
            Publisher’s Note: AccScience
            Publishing remains neutral with
            regard to jurisdictional claims in
            published maps and institutional   Keywords: Mice; Fractionated irradiation; Wound; Collagen; DNA; Glutathione
            affiliations





            Volume 11 Issue 1 (2025)                        34                            doi: 10.36922/jctr.24.00049
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