Topical Deferoxamine Alleviates Skin Injury and Normalizes Atomic Force Microscopy Patterns Following Radiation in a Murine Breast Reconstruction Model

Snider, Alicia; Lynn, Jeremy V.; Urlaub, Kevin M.; Donneys, Alexis; Polyatskaya, Yekaterina; Nelson, Noah S.; Ettinger, Ruth A.; Gurtner, Geoffrey C.; Holl, Mark M. Banaszak; Buchman, Steven R.

doi:10.1097/sap.0000000000001592

Cited by 16 publications

(22 citation statements)

References 28 publications

(41 reference statements)

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“…DFO's therapeutic effects are thought to be mediated through two major mechanisms: (1) a reduction in iron-mediated reactive oxygen species (ROS) generation through its iron scavenging properties resulting in reduced oxidative stress and inflammation and (2) stabilization of hypoxia-inducible factor 1α (HIF1α), a potent transcription factor for numerous pro-angiogenic genes, resulting in improved tissue vascularization. DFO has also been shown to improve collagen deposition and fibril organization in numerous studies [15,18,19].…”

Section: Introductionmentioning

confidence: 99%

Transdermal deferoxamine administration improves excisional wound healing in chronically irradiated murine skin

et al. 2022

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Background Radiation-induced skin injury is a well-known risk factor for impaired wound healing. Over time, the deleterious effects of radiation on skin produce a fibrotic, hypovascular dermis poorly suited to wound healing. Despite increasing understanding of the underlying pathophysiology, therapeutic options remain elusive. Deferoxamine (DFO), an iron-chelating drug, has been shown in prior murine studies to ameliorate radiation-induced skin injury as well as improve wound healing outcomes in various pathologic conditions when administered transdermally. In this preclinical study, we evaluated the effects of deferoxamine on wound healing outcomes in chronically irradiated murine skin. Methods Wild-type mice received 30 Gy of irradiation to their dorsal skin and were left to develop chronic fibrosis. Stented excisional wounds were created on their dorsal skin. Wound healing outcomes were compared across 4 experimental conditions: DFO patch treatment, vehicle-only patch treatment, untreated irradiated wound, and untreated nonirradiated wounds. Gross closure rate, wound perfusion, scar elasticity, histology, and nitric oxide assays were compared across the conditions. Results Relative to vehicle and untreated irradiated wounds, DFO accelerated wound closure and reduced the frequency of healing failure in irradiated wounds. DFO augmented wound perfusion throughout healing and upregulated angiogenesis to levels observed in nonirradiated wounds. Histology revealed DFO increased wound thickness, collagen density, and improved collagen fiber organization to more closely resemble nonirradiated wounds, likely contributing to the observed improved scar elasticity. Lastly, DFO upregulated inducible nitric oxide synthase and increased nitric oxide production in early healing wounds. Conclusion Deferoxamine treatment presents a potential therapeutic avenue through which to target impaired wound healing in patients following radiotherapy.

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Section: Introductionmentioning

confidence: 99%

Transdermal deferoxamine administration improves excisional wound healing in chronically irradiated murine skin

et al. 2022

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“…DFO has promise as a safe, effective treatment with the potential to fill this void, but uncertainty remains regarding the best delivery route. Recently, topical administration of DFO has been studied in wound‐healing experiments 22‐25 22 .…”

Section: Introductionmentioning

confidence: 99%

A comparative analysis of deferoxamine treatment modalities for dermal radiation‐induced fibrosis

Lavin

Abbas

Fahy

et al. 2021

J Cellular Molecular Medi

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The iron chelator, deferoxamine (DFO), has been shown to potentially improve dermal radiation‐induced fibrosis (RIF) in mice through increased angiogenesis and reduced oxidative damage. This preclinical study evaluated the efficacy of two DFO administration modalities, transdermal delivery and direct injection, as well as temporal treatment strategies in relation to radiation therapy to address collateral soft tissue fibrosis. The dorsum of CD‐1 nude mice received 30 Gy radiation, and DFO (3 mg) was administered daily via patch or injection. Treatment regimens were prophylactic, during acute recovery, post‐recovery, or continuously throughout the experiment (n = 5 per condition). Measures included ROS‐detection, histology, biomechanics and vascularity changes. Compared with irradiated control skin, DFO treatment decreased oxidative damage, dermal thickness and collagen content, and increased skin elasticity and vascularity. Metrics of improvement in irradiated skin were most pronounced with continuous transdermal delivery of DFO. In summary, DFO administration reduces dermal fibrosis induced by radiation. Although both treatment modalities were efficacious, the transdermal delivery showed greater effect than injection for each temporal treatment strategy. Interestingly, the continuous patch group was more similar to normal skin than to irradiated control skin by most measures, highlighting a promising approach to address detrimental collateral soft tissue injury following radiation therapy.

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“…Anyway, many other scientific groups demonstrated DFO to be suitable for topical application, specifically to ameliorate cutaneous chronic wounds [ 58 ], radiation-induced soft tissue injury [ 59 ], alleviate skin injury [ 60 ] and to prevent pressure-induced diabetic ulcers [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

Deferoxamine Treatment Improves Antioxidant Cosmeceutical Formulation Protection against Cutaneous Diesel Engine Exhaust Exposure

et al. 2021

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Skin is one of the main targets of the outdoor stressors. Considering that pollution levels are rising progressively, it is not surprising that several cutaneous conditions have been associated with its exposure. Among the pollutants, diesel engine exhaust (DEE) represents one of the most toxic, as it is composed of a mixture of many different noxious chemicals generated during the compression cycle, for ignition rather than an electrical spark as in gasoline engines. The toxic chemicals of most concern in DEE, besides the oxides of nitrogen, sulfur dioxide and various hydrocarbons, are metals that can induce oxidative stress and inflammation. The present study aimed to evaluate the effects of topical application, singularly or in combination, of the iron-chelator deferoxamine and a commercially available formulation, CE Ferulic, in up to 4-day DEE-exposed skin. DEE induced a significant increase in the oxidative marker 4-hydroxy-nonenal (4HNE) and matrix-metallopeptidase-9 (MMP-9), the loss of cutaneous-barrier-associated proteins (filaggrin and involucrin) and a decrease in collagen-1, while the formulations prevented the cutaneous damage in an additive manner. In conclusion, this study suggests that iron plays a key role in DEE-induced skin damage and its chelation could be an adjuvant strategy to reinforce antioxidant topical formulations.

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Topical Deferoxamine Alleviates Skin Injury and Normalizes Atomic Force Microscopy Patterns Following Radiation in a Murine Breast Reconstruction Model

Cited by 16 publications

References 28 publications

Transdermal deferoxamine administration improves excisional wound healing in chronically irradiated murine skin

Transdermal deferoxamine administration improves excisional wound healing in chronically irradiated murine skin

A comparative analysis of deferoxamine treatment modalities for dermal radiation‐induced fibrosis

Deferoxamine Treatment Improves Antioxidant Cosmeceutical Formulation Protection against Cutaneous Diesel Engine Exhaust Exposure

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