Page 53 - JCTR-11-1

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

different doses of fractionated γ-radiation. Hesperidin cannot be ruled out in this study, as long bones of hind
8,34
treatment has been shown to enhance collagen deposition limbs were irradiated during fractionated irradiation.
and vascular and fibroblast densities while decreasing Wounding and irradiation induce oxidative stress,
hyalinization in excision wounds of mice exposed to and their combined effects can further complicate tissue
various doses of whole-body or hemi-body γ-radiation. conditions, as observed in this study. The evaluation
9,10
Ascorbic acid and curcumin have shown similar effects in of antioxidant status in irradiated wounds revealed
irradiated wounds of mice. 79,80,85,95
an increase in LPx, consistent with previous studies
The response of normal tissues to radiation can be that ionizing radiations induce LPx. 115,116 Fractionated
viewed as two concurrent phenomena. The first shares irradiation negatively impacted antioxidant status,
common features with traumatic wound healing, resulting in a significant decline in GSH concentration
perturbed by radiation treatment. The second involves and GSHPx activities in this study. A similar effect has
temporary or permanent changes to extracellular and been reported earlier in the regenerating wounds of
cellular components in the exposed area, potentially mice receiving fractionated irradiation. 115,116 Exposure to
leading to progressive injury over time. Unlike physical different doses of γ-radiation has been reported to reduce
trauma, fractionated radiation therapy produces a series of GSHPx activities and GSH concentration. 36,117 Hesperidin
repeated insults to tissues, altering normal tissue responses pre-treatment protected against radiation-induced LPx and
with each dose fraction. Repetitive radiation exposure mitigated the decline in GSHPx activity and GSH levels.
118
exacerbates, suppresses, or substantially alters cellular Ascorbic acid and curcumin have been reported to arrest
and molecular responses compared to single radiation the decline in GSHpx and GSH contents and reduce LPx
exposure or traumatic injury. The detrimental effects of after fractionated γ-radiation. 115,116 Nigella sativa has been
ionizing radiation on wound healing are multifaceted, found to suppress radiation-induced declines in GSH and
including direct cytotoxic effects on various cellular and GSHpx in regenerating excision wounds of mice exposed
molecular components of wound repair and indirect to whole-body γ-radiation and reduce LPx.
effects through the production of free radicals, which cause
DNA damage and alter proteins, lipids, carbohydrates, The exact mechanism by which hesperidin enhanced
and other complex molecules involved in tissue repair the healing of irradiated wounds is not clearly understood.
and regeneration. 8-13,21,34,79,80,85,95 Even benign injuries However, the pleiotropic action of hesperidin may be
may become lethal when exposed to repeated low doses responsible for early repair and regeneration of irradiated
of radiation. Ionizing radiation severely damages vital wounds. The acceleration in wound healing after hesperidin
tissues, especially those with high cell division rates, such treatment may not be due to a single mechanism but
as the hematopoietic system. 103-105 The loss of significant rather an interplay of several mechanisms during wound
bone marrow cells can lead to immunosuppression, healing. Reactive oxygen species play a fundamental
making individuals susceptible to bacterial infections role in tissue repair, and hesperidin may have reduced
and complicating wound healing. Shielding bone marrow radiation- and wound injury-induced free radicals to
during acute whole-body X-irradiation has been reported optimal levels, facilitating early wound closure. Hesperidin
to reduce mortality and enhance wound closure in rats. passivates free radicals and elevates catalase, GSHPx, and
106
These studies suggest that radiation-sensitive, bone superoxide dismutase, resulting in accelerated wound
marrow-derived cells are crucial for tissue repair. Another healing. 118-120 Hesperidin may have upregulated molecular
possibility includes delayed fixation of the wound edge to events essential for wound repair, including collagen, NO,
underlying tissue due to reduced fibroblast proliferation and DNA synthesis, leading to early repair. In this study,
and synthetic function in the granulation bed. Wound hesperidin was found to increase collagen, NO, and DNA
contraction is a function of contractile fibroblasts, known contents in mice wounds. It acts as an antioxidant, anti-
as myofibroblasts. 107-109 Irradiation impairs wound healing inflammatory, and antimicrobial agent, contributing to the
in the skin by affecting fibroblasts through cytotoxic effects early healing of irradiated wounds. 37,121,122 This contention
on fibroblasts and delaying cell cycle progression. 15,110,111 is supported by the fact that hesperidin increased the
Radiation may also impact fibroblasts through bone marrow antioxidant levels and reduced LPx in the present
depression, as some fibroblasts in normal subcutaneous study. Hesperidin enhances fibroblast proliferation and
connective tissue participating in wound healing originate vasculature, leading to early wound closure. Although
from the bone marrow. 17,112,113 Recent studies suggest that the molecular mechanisms of hesperidin’s actions on
vascular cell progenitors residing in the bone marrow irradiated wounds were not investigated, it is hypothesized
contribute to blood vessel formation during tissue repair to modulate the NF-κB signaling pathway. NF-κB is a
and in other pathological conditions. A similar effect key regulatory molecule whose transcriptional activation
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Volume 11 Issue 1 (2025) 47 doi: 10.36922/jctr.24.00049