Page 41 - JCTR-11-1

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

1. Introduction Vitamin A supplementation has been reported to inhibit
acute radiation-induced defects in wound healing,
Ionizing radiation is an important treatment modality for likely by promoting an early inflammatory response and
various neoplastic disorders, with approximately 50% of increasing the presence of monocytes and macrophages
cancer patients undergoing fractionated radiotherapy as at the wound site. Certain radioprotective compounds,
28
1
either a curative or palliative approach. The therapeutic including mercaptoethylamine, serotonin, and WR 2721,
efficiency of radiation in cancer treatment is enhanced by have also proven useful in managing combined injuries.
29
administering 20 – 30 fractions, each delivering 2 – 3 Gy, Furthermore, several growth factors and antimicrobial agents
over 5 – 6 weeks. Despite its significant therapeutic benefits, have been explored in animal models as potential options
normal skin is invariably subjected to the cytotoxic effects to improve wound healing in radiation-damaged skin. 30-33
2,3
of radiation. In addition, fractionated radiotherapy is
frequently utilized as a palliative treatment following the Wound-healing abnormalities can inflict significant
3,4
surgical resection of tumors. Investigating the impact physical and psychological trauma on affected patients,
of irradiation on wound repair and regeneration is resulting in high treatment costs. Therefore, exploring
essential for improving cure rates among cancer patients. new pharmacological agents that may help mitigate these
Wound healing involves a complex sequence of well- wound-healing complications is essential. The use of
coordinated cellular and molecular events, encompassing nutraceuticals in the reconstruction of irradiated wounds
inflammation, angiogenesis, fibroplasia, wound presents a promising avenue, as they are widely accepted,
5-7
contraction, epithelialization, and matrix remodeling. well-tolerated, cost-effective, and can be safely utilized
When wounded tissue is exposed to ionizing radiation, in human applications. 34-36 Hesperidin (hesperetin-
the normal physiological responses to injury are disrupted, 7-rhamnoglucoside or hesperetin-7-rutinoside), a
resulting in an extended recovery period. The effects of predominant citrus bioflavonoid found in sweet oranges
ionizing radiation on the skin lead to multiple detrimental (Citrus sinensis) and tangelos, has demonstrated various
effects on wound healing processes. Specifically, ionizing beneficial properties, including anti-inflammatory,
radiation not only impairs inflammatory responses that analgesic, antihypertensive, diuretic, antibacterial, and
are critical to wound repair, but also adversely affects antiviral effects across multiple studies. 37-43 Furthermore,
connective tissue proliferation, granulation tissue it has been reported to inhibit tumor initiation and
formation maturation, collagen mRNA transcription, promotion while reversing the neoplastic transformation
collagen secretion, and revascularization. 8-13 Moreover, in vitro and in vivo. 40,44-46 Hesperidin has also been
ionizing radiation hinders collagen synthesis and delays found to reduce human cholesterol levels and slow bone
the maturation of collagen fibers, 8-10,14 Infections resulting loss. 40,47,48 Deficiency of hesperidin has been associated
from radiation-induced bone marrow suppression can with abnormal capillary leakage and exhibits beneficial
further complicate the recovery of irradiated wounds. effects on capillary permeability and fragility, protecting
The replicative capacity of fibroblasts within irradiated against various traumas, stresses, and cardiotoxicity. 49-51
tissues may be diminished or selectively reduced due to Importantly, hesperidin is non-toxic in animals and
the destruction of rapidly proliferating fibroblasts post- humans. In addition, it offers protection against
52
irradiation. 15-20 In addition, exposure to ionizing radiation chemical-induced toxicity. 52-56 Similarly, a micronized
has been reported to reduce the tensile strength of newly flavonoid fraction containing 90% diosmin and 10%
generated skin wounds. 21-23 hesperidin has been reported to protect against reactive
Several attempts have been made to identify potential oxygen radicals both in vivo and in vitro. This fraction
therapeutic approaches aimed at enhancing the healing has proven effective in promoting the healing of clean and
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of irradiated wounds. Hydrogel and hydrocolloid gel infected wounds through oral and topical administration.
dressings have been utilized to alleviate wound discomfort Hesperidin also exerts anticancer, antiobesity, antioxidant,
and reduce wound healing time in radiation-induced and radioprotective actions. 38,58-62 Both hesperidin and its
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ulcers. Sucralfate octasulfate, a persulfated disaccharide, aglycone hesperetin are recognized for their wide range
has been reported to accelerate the repair and regeneration of pharmacological properties. Given its pleiotropic
of irradiated wounds in animals while mitigating skin effects, non-toxic nature, and significant implications
reactions in humans undergoing radiotherapy. Similar of fractionated radiation on wound repair in healthcare
findings have been observed with pentoxifylline in settings, we conceptualize the present study and investigate
patients receiving radiation therapy. Phenytoin sodium the efficacy of hesperidin treatment in mice partially
25
has demonstrated the ability to enhance the stimulating exposed to varying doses of fractionated γ-radiation while
effects of wound fluid on fibroblast proliferation and subjected to additional trauma through an open deep
collagen synthesis following irradiation. 26,27 In addition, dermal excision wound.

Volume 11 Issue 1 (2025) 35 doi: 10.36922/jctr.24.00049