Author:
Shen Abra H.,Borrelli Mimi R.,Adem Sandeep,Deleon Nestor M. Diaz,Patel Ronak A.,Mascharak Shamik,Yen Sara J.,Sun Blake Y.,Taylor Walter L.,Januszyk Michael,Nguyen Dung H.,Momeni Arash,Gurtner Geoffrey C.,Longaker Michael T.,Wan Derrick C.
Abstract
AbstractRadiation therapy can result in pathological fibrosis of healthy soft tissue. The iron chelator deferoxamine (DFO) has been shown to improve skin vascularization when injected into radiated tissue prior to fat grafting. Here, we evaluated whether topical DFO administration using a transdermal drug delivery system prior to and immediately following irradiation (IR) can mitigate the chronic effects of radiation damage to the skin. CD-1 nude immunodeficient mice were split into four experimental groups: (1) IR alone (IR only), (2) DFO treatment for two weeks after recovery from IR (DFO post-IR), (3) DFO prophylaxis with treatment through and post-IR (DFO ppx), or (4) no irradiation or DFO (No IR). Immediately following IR, reactive oxygen species and apoptotic markers were significantly decreased and laser doppler analysis revealed significantly improved skin perfusion in mice receiving prophylactic DFO. Six weeks following IR, mice in the DFO post-IR and DFO ppx groups had improved skin perfusion and increased vascularization. DFO-treated groups also had evidence of reduced dermal thickness and collagen fiber network organization akin to non-irradiated skin. Thus, transdermal delivery of DFO improves tissue perfusion and mitigates chronic radiation-induced skin fibrosis, highlighting a potential role for DFO in the treatment of oncological patients.
Funder
Sarnoff Cardiovascular Research Foundation
Plastic Surgery Research Foundation
California Institute for Regenerative Medicine
National Institutes of Health
National Institutes of Health,United States
Steinhart/Reed Fund
Gunn/Olivier Research Fund
Publisher
Springer Science and Business Media LLC
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