Page 52 - JCTR-11-1

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

tissue. It is essential for triggering inflammatory a multifaceted signaling molecule that drives cellular
89
responses, mitogenesis, and cellular differentiation, as metabolism, inflammation, and cell stress responses. NO
well as promoting the synthesis of inflammatory cytokines exerts its effects through S-nitrosylation, binding to thiol
during wound healing. 90,91 A balance between collagen proteins and non-protein molecules, which is essential
96
synthesis and degradation is crucial during normal for its protective or toxic effects. Most evidence suggests
wound healing as excess collagen formation can lead that sufficient NO synthesis is required to promote
to keloid formation and hypertrophic scar formation, processes central to wound healing, such as inflammation,
whereas insufficient collagen synthesis may result in angiogenesis, fibroblast synthetic function, epithelial
wound dehiscence and chronic non-healing wounds/ cell proliferation, regulation of collagen formation, and
ulcers. 92,93 Collagen, primarily produced by fibroblasts, is wound contraction. 57,97,98 Estimation of nitrite or nitrate
a key molecule in the extracellular matrix of the wound levels serves as a measure of NO production. Nitrite
99
bed, assisting in the acquisition of tensile strength during levels, a stable end-product of NO synthesis, are elevated
wound repair. The reduction in hydroxyproline content early and transiently in fluid obtained from sponges
94
58
in granulation tissue following fractionated irradiation implanted in subcutaneous wounds. The estimation of
indicates a depletion in collagen synthesis and retardation nitrate and nitrite levels in excision wounds of irradiated
in wound repair and regeneration. An identical effect has mice shows a reduction in NO synthesis. A similar effect
been observed previously, where irradiation with different has been reported in cutaneous excision wounds of mice
doses of fractionated γ-radiation resulted in a dose- receiving different doses of fractionated irradiation or
dependent reduction in collagen synthesis. Increasing acute whole-body or hemi-body exposure. The reduction
8,34
doses of γ-radiation have been reported to progressively in NO expression has been correlated with radiation-
destroy native collagen synthesis. 79,80,85,86 Hesperidin induced impairment of wound healing. 8,34,36,79,80,86,95,100
administration before irradiation mitigated the radiation- Administration of hesperidin before irradiation elevated
induced decrease in collagen synthesis at all post- nitrite levels. In earlier studies, hesperidin significantly
irradiation days. Similarly, ascorbic acid and curcumin increased nitrite and nitrate levels in wound granulation
have been shown to counteract the radiation-induced tissue of acute whole-body or hemi-body irradiated
decline in collagen synthesis in regenerating wounds mice. 9,83,84 Similarly, ascorbic acid and curcumin increased
exposed to fractionated γ-irradiation. Hesperidin nitrite and nitrate levels in open excision wounds of mice
8,34
treatment has been reported to increase collagen synthesis exposed to different doses of fractionated, acute whole,
in excision wounds of mice. 9,10,83,84 Ascorbic acid, curcumin, or hemi-body γ-irradiation, facilitating early healing of
8,34,79,80,86,95
and Nigella sativa extract have also been found to increase irradiated wounds.
collagen synthesis in irradiated wounds. 36,79,80,86,95 Histological observations align with biochemical
The estimation of DNA contents in wounds serves as estimations, revealing a decrease in collagen deposition,
a measure of cell proliferation, indicating regeneration which is further supported by reduced fibroblast
and repair of wounds. 79,80,85,86 Fractionated irradiation proliferation – cells responsible for collagen synthesis.
causes a dose-dependent reduction in DNA synthesis. An identical effect has been observed previously, where
8,34
A similar alleviation in DNA synthesis has been reported exposure of mice to fractionated irradiation inhibited
in regenerating wounds of mice exposed to different doses fibroblast proliferation, neovascularization, and collagen
8,34
of γ-radiation. 79,80,85,86 Hesperidin treatment significantly deposition in regenerating wounds. Irradiation
increased DNA content at days 4 and 8 post-irradiation. has been reported to impede fibroblast proliferation,
Hesperidin administration has been shown to enhance neovascularization, and collagen deposition in regenerating
100
DNA synthesis in regenerating wounds of mice created wounds. Similarly, total-body and hemi-body irradiation
after whole-body or hemi-body irradiation. 9,10,83,84 Ascorbic decreased cellular influx, vascularization, fibroblast density,
Cell culture
and collagen deposition in mice.
21,79,80,85,95,101
acid, curcumin, or Nigella sativa methanol extract studies of fibroblasts exposed to fractionated ionizing
treatment of mice before whole/hemi-body or fractionated radiation have also demonstrated a decline in fibroblasts.
102
irradiation has been reported to increase DNA synthesis in Pre-treatment of mice with hesperidin improved collagen
granulation tissues of excision wounds. 8,36,79,80,85,86,95 deposition, increased vascular and fibroblast density, and
Inflammatory responses are critical for proper reduced hyalinization in the hesperidin + irradiation
and smooth wound repair and regeneration, elicited group. Ascorbic acid and curcumin have been reported
immediately after injury through a series of well- to augment collagen deposition, and vascular and
orchestrated cellular and biochemical events. These events fibroblast densities, as well as reduce hyalinization in
include increased synthesis of NO or nitrogen monoxide, open regenerating excision wounds of mice receiving

Volume 11 Issue 1 (2025) 46 doi: 10.36922/jctr.24.00049