Page 51 - JCTR-11-1

Journal of Clinical and
Translational Research Hesperidin enhances repair of γ-irradiated wounds

used alone or in combination with surgery or other
modalities for treating neoplastic disorders. However,
radiotherapy poses a critical challenge: it must balance the
eradication of cancerous cells with the adverse effects on
surrounding non-neoplastic tissues. This dichotomy raises
significant concerns for surgeons regarding the malignant
potential of irradiated tissue beds and wound-healing
complications. 73-76 Given these challenges, it is imperative
to explore new strategies that can mitigate the deleterious
effect of ionizing radiation on normal tissue while
enhancing wound repair and regeneration. Hesperidin,
a dietary flavanone, has been investigated for its wound-
healing potential in mice exposed to different doses of
fractionated γ-irradiation and subsequently inflicted with
full-thickness open excision wounds.
Figure 9. Effect of hesperidin on the fibroblast density in the granulation
tissue of regenerating deep dermal wound of mice exposed to different Wound contraction, defined as the centripetal
doses of fractionated γ- radiation at different post-irradiation times. HPD movement of wound edges facilitating defect closure, 8,77,78
groups are compared to the CMC and SIR groups. serves as a key indicator of wound healing progression.
Abbreviations: CMC: Carboxymethylcellulose; HPD: Hesperidin; Periodic assessment of wound contraction allows for
SIR: Sham-irradiation.
evaluating healing progress. 8,9,77,78 Exposure of mice to
different doses of fractionated γ-radiation delays wound
contraction and increases the MHT in a dose-dependent
manner, with the maximum delay observed after 40 Gy
irradiation. Previously, fractionated irradiation was
found to delay wound contraction and MHT in a dose-
dependent manner. 8,34,79 This dose-dependent delay in
wound contraction and MHT suggests alterations in
the local wound milieu, leading to impaired wound
repair and regeneration. 8,9,34,79-82 Administration of
100 mg/kg body weight of hesperidin before exposure
to fractionated radiation elicited enhanced regenerative
responses, characterized by increased wound contraction
and reduced MHT. Previous studies have shown that
hesperidin enhances wound contraction and shortens
MHT in deep dermal excision wounds of whole-body or
hemi-body-irradiated mice. Similarly, topical application
Figure 10. Effect of hesperidin on the blood vessel density in the of hesperidin hydrogel has been effective in irradiated
granulation tissue of regenerating deep dermal wound of mice exposed 9,10,83,84
to different doses of fractionated γ- radiation at different post-irradiation mice wounds. Other compounds, such as ascorbic
times. HPD groups are compared to the CMC and SIR groups. acid and curcumin, have also been reported to augment
Abbreviations: CMC: Carboxymethylcellulose; HPD: Hesperidin; regenerative responses in irradiated wounds by
8,34
SIR: Sham-irradiation. enhancing wound contraction and alleviating MHT in
the deep dermal excision wound of mice. 79,80,85,86 A similar
4. Discussion effect was discernible in the irradiated wounds of mice
87
The increasing use of radioactive materials in various receiving topical application of curcumin hydrogel. In
sectors, including industry, medicine, science, military, addition, sildenafil citrate and antigen α-gal (Galα1-
and localized areas of high radiation within nuclear 3Galβ1-(3)4GlcNAc-R) nanoparticles hydrogel gel have
facilities, has significantly increased the risk of large- been shown to enhance wound contraction and tensile
23,88
scale, uncontrolled exposure to radiation, especially strength, while Vitamin A supplementation has reduced
28
during accidents. In addition, the potential for deliberate radiation-induced delays in wound healing.
misuse of radioactive material by terrorists cannot Collagen plays a pivotal role in wound healing, as it is
be dismissed. 8,9,70-72 Hemi-body irradiation, often a principal component of connective tissue, providing a
administered in multiple fractionated doses, is frequently structural framework, strength, and milieu for regenerating

Volume 11 Issue 1 (2025) 45 doi: 10.36922/jctr.24.00049