Prophylactic treatment with transdermal deferoxamine mitigates radiation-induced skin fibrosis.

Autor: Shen AH; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic Surgery, Department of Surgery, Stanford University School of Medicine, 257 Campus Drive, Stanford, CA, 94305-5148, USA., Borrelli MR; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic Surgery, Department of Surgery, Stanford University School of Medicine, 257 Campus Drive, Stanford, CA, 94305-5148, USA., Adem S; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic Surgery, Department of Surgery, Stanford University School of Medicine, 257 Campus Drive, Stanford, CA, 94305-5148, USA., Deleon NMD; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic Surgery, Department of Surgery, Stanford University School of Medicine, 257 Campus Drive, Stanford, CA, 94305-5148, USA., Patel RA; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic Surgery, Department of Surgery, Stanford University School of Medicine, 257 Campus Drive, Stanford, CA, 94305-5148, USA., Mascharak S; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic Surgery, Department of Surgery, Stanford University School of Medicine, 257 Campus Drive, Stanford, CA, 94305-5148, USA., Yen SJ; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic Surgery, Department of Surgery, Stanford University School of Medicine, 257 Campus Drive, Stanford, CA, 94305-5148, USA., Sun BY; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic Surgery, Department of Surgery, Stanford University School of Medicine, 257 Campus Drive, Stanford, CA, 94305-5148, USA., Taylor WL 4th; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic Surgery, Department of Surgery, Stanford University School of Medicine, 257 Campus Drive, Stanford, CA, 94305-5148, USA., Januszyk M; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic Surgery, Department of Surgery, Stanford University School of Medicine, 257 Campus Drive, Stanford, CA, 94305-5148, USA., Nguyen DH; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic Surgery, Department of Surgery, Stanford University School of Medicine, 257 Campus Drive, Stanford, CA, 94305-5148, USA., Momeni A; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic Surgery, Department of Surgery, Stanford University School of Medicine, 257 Campus Drive, Stanford, CA, 94305-5148, USA., Gurtner GC; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic Surgery, Department of Surgery, Stanford University School of Medicine, 257 Campus Drive, Stanford, CA, 94305-5148, USA., Longaker MT; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic Surgery, Department of Surgery, Stanford University School of Medicine, 257 Campus Drive, Stanford, CA, 94305-5148, USA.; Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA., Wan DC; Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic Surgery, Department of Surgery, Stanford University School of Medicine, 257 Campus Drive, Stanford, CA, 94305-5148, USA. dwan@stanford.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2020 Jul 23; Vol. 10 (1), pp. 12346. Date of Electronic Publication: 2020 Jul 23.
DOI: 10.1038/s41598-020-69293-4
Abstrakt: Radiation 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.
Databáze: MEDLINE
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