دورية أكاديمية
Prophylactic treatment with transdermal deferoxamine mitigates radiation-induced skin fibrosis.
العنوان: | Prophylactic treatment with transdermal deferoxamine mitigates radiation-induced skin fibrosis. |
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المؤلفون: | 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. |
المصدر: | Scientific reports [Sci Rep] 2020 Jul 23; Vol. 10 (1), pp. 12346. Date of Electronic Publication: 2020 Jul 23. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: London : Nature Publishing Group, copyright 2011- |
مواضيع طبية MeSH: | Deferoxamine/*pharmacology , Dermis/*metabolism , Radiation Injuries, Experimental/*prevention & control , Radiodermatitis/*prevention & control, Animals ; Dermis/pathology ; Female ; Mice ; Mice, Nude ; Radiation Injuries, Experimental/metabolism ; Radiation Injuries, Experimental/pathology ; Radiodermatitis/metabolism ; Radiodermatitis/pathology |
مستخلص: | 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. |
References: | Delaney, G., Jacob, S., Featherstone, C. & Barton, M. The role of radiotherapy in cancer treatment: estimating optimal utilization from a review of evidence-based clinical guidelines. Cancer Interdiscip. Int. J. Am. Cancer Soc. 104, 1129–1137 (2005). Goldschmidt, H. & Sherwin, W. K. Reactions to ionizing radiation. J. Am. Acad. Dermatol. 3, 551–579 (1980). (PMID: 10.1016/S0190-9622(80)80067-3) Bentzen, S. R. M. & Thames, H. D. Incidence and latency of radiation reactions. Radiother. Oncol. 14, 261–262 (1989). (PMID: 10.1016/0167-8140(89)90174-6) Thanik, V. D. et al. A novel mouse model of cutaneous radiation injury. Plast. Reconstr. Surg. 127, 560–568 (2011). (PMID: 10.1097/PRS.0b013e3181fed4f7) Chin, M. S. et al. Skin perfusion and oxygenation changes in radiation fibrosis. Plast. Reconstr. Surg. 131, 707–716 (2013). (PMID: 10.1097/PRS.0b013e3182818b94) Tadjalli, H. E. et al. Skin graft survival after external beam irradiation. Plast. Reconstr. Surg. 103, 1902–1908 (1999). (PMID: 10.1097/00006534-199906000-00015) Borrelli, M. R. et al. Radiation-induced skin fibrosis: pathogenesis, current treatment options, and emerging therapeutics. Ann. Plast. Surg. 83, S59–S64 (2019). (PMID: 10.1097/SAP.0000000000002098) Khodamoradi, E. et al. Targets for protection and mitigation of radiation injury. Cell Mol. Life Sci. https://doi.org/10.1007/s00018-020-03479-x (2020). (PMID: 10.1007/s00018-020-03479-x32072238) Straub, J. M. et al. Radiation-induced fibrosis: mechanisms and implications for therapy. J. Cancer Res. Clin. Oncol. 141, 1985–1994. https://doi.org/10.1007/s00432-015-1974-6 (2015). (PMID: 10.1007/s00432-015-1974-6259109884573901) Citrin, D. E. et al. Radiation-induced fibrosis: mechanisms and opportunities to mitigate: report of an NCI Workshop, September 19, 2016. Radiat Res 188, 1–20. https://doi.org/10.1667/RR14784.1 (2017). (PMID: 10.1667/RR14784.1284894885558616) Martin, M., Lefaix, J.-L. & Delanian, S. TGF-β1 and radiation fibrosis: a master switch and a specific therapeutic target?. Int. J. Radiat. Oncol. Biol. Phys. 47, 277–290 (2000). (PMID: 10.1016/S0360-3016(00)00435-1) Westbury, C. & Yarnold, J. Radiation fibrosis—current clinical and therapeutic perspectives. Clin. Oncol. 24, 657–672 (2012). (PMID: 10.1016/j.clon.2012.04.001) Baker, D. G. & Krochak, R. J. The response of the microvascular system to radiation: a review. Cancer Invest. 7, 287–294 (1989). (PMID: 10.3109/07357908909039849) Incalza, M. A. et al. Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases. Vascul. Pharmacol 100, 1–19. https://doi.org/10.1016/j.vph.2017.05.005 (2018). (PMID: 10.1016/j.vph.2017.05.00528579545) Craige, S. M., Kant, S. & Keaney, J. F. Jr. Reactive oxygen species in endothelial function: from disease to adaptation. Circ. J. 79, 1145–1155. https://doi.org/10.1253/circj.CJ-15-0464 (2015). (PMID: 10.1253/circj.CJ-15-046425986771) Nedeljkovic, Z. S., Gokce, N. & Loscalzo, J. Mechanisms of oxidative stress and vascular dysfunction. Postgrad Med. J. 79, 195–199. https://doi.org/10.1136/pmj.79.930.195 (2003). (PMID: 10.1136/pmj.79.930.195127433341742679) Shrishrimal, S., Kosmacek, E. A. & Oberley-Deegan, R. E. Reactive oxygen species drive epigenetic changes in radiation-induced fibrosis. Oxid. Med. Cell Longev. 2019, 4278658. https://doi.org/10.1155/2019/4278658 (2019). (PMID: 10.1155/2019/4278658308815916381575) Wlaschek, M., Singh, K., Sindrilaru, A., Crisan, D. & Scharffetter-Kochanek, K. Iron and iron-dependent reactive oxygen species in the regulation of macrophages and fibroblasts in non-healing chronic wounds. Free Radic. Biol. Med. 133, 262–275. https://doi.org/10.1016/j.freeradbiomed.2018.09.036 (2019). (PMID: 10.1016/j.freeradbiomed.2018.09.03630261274) Sindrilaru, A. et al. An unrestrained proinflammatory M1 macrophage population induced by iron impairs wound healing in humans and mice. J Clin Invest 121, 985–997. https://doi.org/10.1172/JCI44490 (2011). (PMID: 10.1172/JCI44490213175343049372) Pham, N. et al. Topical esomeprazole mitigates radiation-induced dermal inflammation and fibrosis. Radiat Res 192, 473–482. https://doi.org/10.1667/RR15398.1 (2019). (PMID: 10.1667/RR15398.131415221) Kehrer, J. P. The Haber-Weiss reaction and mechanisms of toxicity. Toxicology 149, 43–50. https://doi.org/10.1016/s0300-483x(00)00231-6 (2000). (PMID: 10.1016/s0300-483x(00)00231-610963860) Winterbourn, C. C. Toxicity of iron and hydrogen peroxide: the Fenton reaction. Toxicol. Lett. 82–83, 969–974. https://doi.org/10.1016/0378-4274(95)03532-x (1995). (PMID: 10.1016/0378-4274(95)03532-x8597169) Ryan, T. P. & Aust, S. D. The role of iron in oxygen-mediated toxicities. Crit. Rev. Toxicol. 22, 119–141. https://doi.org/10.3109/10408449209146308 (1992). (PMID: 10.3109/104084492091463081510819) Redza-Dutordoir, M. & Averill-Bates, D. A. Activation of apoptosis signalling pathways by reactive oxygen species. Biochim. Biophys. Acta 2977–2992, 2016. https://doi.org/10.1016/j.bbamcr.2016.09.012 (1863). (PMID: 10.1016/j.bbamcr.2016.09.012) Heli, H., Mirtorabi, S. & Karimian, K. Advances in iron chelation: an update. Expert Opin. Ther. Pat. 21, 819–856. https://doi.org/10.1517/13543776.2011.569493 (2011). (PMID: 10.1517/13543776.2011.56949321449664) Teppo, H. R., Soini, Y. & Karihtala, P. Reactive oxygen species-mediated mechanisms of action of targeted cancer therapy. Oxid. Med. Cell. Longev. 2017, 1485283. https://doi.org/10.1155/2017/1485283 (2017). (PMID: 10.1155/2017/1485283286987655494102) Budzyn, M. et al. Serum iron concentration and plasma oxidant-antioxidant balance in patients with chronic venous insufficency. Med. Sci. Monit. 17, 719–727. https://doi.org/10.12659/msm.882132 (2011). (PMID: 10.12659/msm.882132) Yeoh-Ellerton, S. & Stacey, M. C. Iron and 8-isoprostane levels in acute and chronic wounds. J. Invest. Dermatol. 121, 918–925. https://doi.org/10.1046/j.1523-1747.2003.12471.x (2003). (PMID: 10.1046/j.1523-1747.2003.12471.x14632213) Wenk, J. et al. Selective pick-up of increased iron by deferoxamine-coupled cellulose abrogates the iron-driven induction of matrix-degrading metalloproteinase 1 and lipid peroxidation in human dermal fibroblasts in vitro: a new dressing concept. J. Invest. Dermatol. 116, 833–839. https://doi.org/10.1046/j.1523-1747.2001.01345.x (2001). (PMID: 10.1046/j.1523-1747.2001.01345.x11407968) Wright, J. A., Richards, T. & Srai, S. K. The role of iron in the skin and cutaneous wound healing. Front. Pharmacol. 5, 156. https://doi.org/10.3389/fphar.2014.00156 (2014). (PMID: 10.3389/fphar.2014.00156250715754091310) Duscher, D. et al. Transdermal deferoxamine prevents pressure-induced diabetic ulcers. Proc. Natl. Acad. Sci. U.S.A. 112, 94–99. https://doi.org/10.1073/pnas.1413445112 (2015). (PMID: 10.1073/pnas.141344511225535360) Shen, X. et al. Prolyl hydroxylase inhibitors increase neoangiogenesis and callus formation following femur fracture in mice. J. Orthop. Res. 27, 1298–1305 (2009). (PMID: 10.1002/jor.20886) Mericli, A. F. et al. Deferoxamine mitigates radiation-induced tissue injury in a rat irradiated TRAM flap model. Plast. Reconstr. Surg. 135, 124e–134e (2015). (PMID: 10.1097/PRS.0000000000000844) Farberg, A. S. et al. Deferoxamine reverses radiation induced hypovascularity during bone regeneration and repair in the murine mandible. Bone 50, 1184–1187 (2012). (PMID: 10.1016/j.bone.2012.01.019) Donneys, A. et al. Deferoxamine expedites consolidation during mandibular distraction osteogenesis. Bone 55, 384–390 (2013). (PMID: 10.1016/j.bone.2013.04.005) Garza, R. M. et al. Studies in Fat Grafting: Part III Fat grafting irradiated tissue: Improved skin quality and decreased fat graft retention. Plast. Reconstr. Surg. 134, 249 (2014). (PMID: 10.1097/PRS.0000000000000326) Luan, A. et al. Cell-assisted lipotransfer improves volume retention in irradiated recipient sites and rescues radiation-induced skin changes. Stem Cells 34, 668–673 (2016). (PMID: 10.1002/stem.2256) Flacco, J. et al. Deferoxamine preconditioning of irradiated tissue improves perfusion and fat graft retention. Plast. Reconstr. Surg. 141, 655–665 (2018). (PMID: 10.1097/PRS.0000000000004167) Wang, Q. & Zou, M. H. Measurement of reactive oxygen species (ROS) and mitochondrial ROS in AMPK knockout mice blood vessels. Methods Mol Biol 1732, 507–517. https://doi.org/10.1007/978-1-4939-7598-3_32 (2018). (PMID: 10.1007/978-1-4939-7598-3_32294804966407612) Driskell, R. R. et al. Distinct fibroblast lineages determine dermal architecture in skin development and repair. Nature 504, 277–281. https://doi.org/10.1038/nature12783 (2013). (PMID: 10.1038/nature12783243362873868929) Mascharak, S. d.-P., H.E.; Borrelli, M.R., Chinta, M.S., Moore, A.L., Kania, G., Titan, A.L., Foster, D.S., Duoto, B.A., Brewer, R.E., Sokol, J., Garibay, E., Lerbs, T., Saleem, A., Devereaux, K., Gurtner, G.C., Lorenz, H.P., Wan, D.C., Distler, O., Chang, H.Y., Wernig, G., Longaker, M.T. Machine learning analysis of connective tissue networks in scarring and chronic fibroses. Article Under Revision for Nature (2020). Borrelli, M. R. et al. Fat grafting rescues radiation-induced joint contracture. Stem cells 38, 382–389. https://doi.org/10.1002/stem.3115 (2020). (PMID: 10.1002/stem.311531793745) Stone, H. B., Coleman, C. N., Anscher, M. S. & McBride, W. H. Effects of radiation on normal tissue: consequences and mechanisms. Lancet Oncol. 4, 529–536 (2003). (PMID: 10.1016/S1470-2045(03)01191-4) Yarnold, J. & Brotons, M.-C.V. Pathogenetic mechanisms in radiation fibrosis. Radiother. Oncol. 97, 149–161 (2010). (PMID: 10.1016/j.radonc.2010.09.002) Falanga, V., Zhou, L. & Yufit, T. Low oxygen tension stimulates collagen synthesis and COL1A1 transcription through the action of TGF-β1. J. Cell. Physiol. 191, 42–50 (2002). (PMID: 10.1002/jcp.10065) Morry, J., Ngamcherdtrakul, W. & Yantasee, W. Oxidative stress in cancer and fibrosis: Opportunity for therapeutic intervention with antioxidant compounds, enzymes, and nanoparticles. Redox. Biol. 11, 240–253. https://doi.org/10.1016/j.redox.2016.12.011 (2017). (PMID: 10.1016/j.redox.2016.12.01128012439) Amini, P., Ashrafizadeh, M., Motevaseli, E., Najafi, M. & Shirazi, A. Mitigation of radiation-induced hematopoietic system injury by melatonin. Environ. Toxicol. https://doi.org/10.1002/tox.22917 (2020). (PMID: 10.1002/tox.2291732125094) Okunieff, P. et al. Pentoxifylline in the treatment of radiation-induced fibrosis. J. Clin. Oncol. 22, 2207–2213 (2004). (PMID: 10.1200/JCO.2004.09.101) Delanian, S., Porcher, R., Balla-Mekias, S. & Lefaix, J.-L. Randomized, placebo-controlled trial of combined pentoxifylline and tocopherol for regression of superficial radiation-induced fibrosis. J. Clin. Oncol. 21, 2545–2550 (2003). (PMID: 10.1200/JCO.2003.06.064) Gothard, L. et al. Double-blind placebo-controlled randomised trial of vitamin E and pentoxifylline in patients with chronic arm lymphoedema and fibrosis after surgery and radiotherapy for breast cancer. Radiother. Oncol. 73, 133–139 (2004). (PMID: 10.1016/j.radonc.2004.09.013) Jacobson, G. et al. Randomized trial of pentoxifylline and vitamin E vs standard follow-up after breast irradiation to prevent breast fibrosis, evaluated by tissue compliance meter. Int. J. Radiat. Oncol. Biol. Phys. 85, 604–608. https://doi.org/10.1016/j.ijrobp.2012.06.042 (2013). (PMID: 10.1016/j.ijrobp.2012.06.04222846413) Famoso, J. M., Laughlin, B., McBride, A. & Gonzalez, V. J. Pentoxifylline and vitamin E drug compliance after adjuvant breast radiation therapy. Adv. Radiat. Oncol. 3, 19–24 (2018). (PMID: 10.1016/j.adro.2017.09.004) Delanian, S., Porcher, R., Rudant, J. & Lefaix, J. L. Kinetics of response to long-term treatment combining pentoxifylline and tocopherol in patients with superficial radiation-induced fibrosis. J. Clin. Oncol. 23, 8570–8579. https://doi.org/10.1200/JCO.2005.02.4729 (2005). (PMID: 10.1200/JCO.2005.02.472916260695) Griffin, M. F., Drago, J., Almadori, A., Kalavrezos, N. & Butler, P. E. Evaluation of the efficacy of lipotransfer to manage radiation-induced fibrosis and volume defects in head and neck oncology. Head Neck 41, 3647–3655. https://doi.org/10.1002/hed.25888 (2019). (PMID: 10.1002/hed.2588831389085) Phulpin, B. et al. Rehabilitation of irradiated head and neck tissues by autologous fat transplantation. Plast. Reconstr. Surg. 123, 1187–1197. https://doi.org/10.1097/PRS.0b013e31819f292800006534-200904000-00006[pii] (2009). (PMID: 10.1097/PRS.0b013e31819f292800006534-200904000-00006[pii]19337087) Gerber, P. A. et al. The top skin-associated genes: a comparative analysis of human and mouse skin transcriptomes. Biol. Chem. 395, 577–591. https://doi.org/10.1515/hsz-2013-0279 (2014). (PMID: 10.1515/hsz-2013-027924497224) Elsea, S. H. & Lucas, R. E. The mousetrap: what we can learn when the mouse model does not mimic the human disease. ILAR J. 43, 66–79. https://doi.org/10.1093/ilar.43.2.66 (2002). (PMID: 10.1093/ilar.43.2.6611917158) Sullivan, T. P., Eaglstein, W. H., Davis, S. C. & Mertz, P. The pig as a model for human wound healing. Wound Repair Regen. 9, 66–76. https://doi.org/10.1046/j.1524-475x.2001.00066.x (2001). (PMID: 10.1046/j.1524-475x.2001.00066.x11350644) Rodrigues, M. et al. Iron chelation with transdermal deferoxamine accelerates healing of murine sickle cell ulcers. Adv. Wound Care (New Rochelle) 7, 323–332. https://doi.org/10.1089/wound.2018.0789 (2018). (PMID: 10.1089/wound.2018.0789) Ma, C. M. et al. AAPM protocol for 40–300 kV x-ray beam dosimetry in radiotherapy and radiobiology. Med Phys 28, 868–893. https://doi.org/10.1118/1.1374247 (2001). (PMID: 10.1118/1.137424711439485) Azzam, E. I., Jay-Gerin, J. P. & Pain, D. Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury. Cancer Lett 327, 48–60. https://doi.org/10.1016/j.canlet.2011.12.012 (2012). (PMID: 10.1016/j.canlet.2011.12.01222182453) Ogawa, Y. et al. Radiation-induced reactive oxygen species formation prior to oxidative DNA damage in human peripheral T cells. Int J Mol Med 11, 149–152 (2003). (PMID: 12525868) |
معلومات مُعتمدة: | DE027346 United States NH NIH HHS; U01 HL099776 United States NH NIH HHS; R01 DE027346 United States DE NIDCR NIH HHS; R01 GM116892 United States GM NIGMS NIH HHS; U24 DE026914 United States DE NIDCR NIH HHS |
المشرفين على المادة: | J06Y7MXW4D (Deferoxamine) |
تواريخ الأحداث: | Date Created: 20200725 Date Completed: 20201208 Latest Revision: 20220716 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC7378074 |
DOI: | 10.1038/s41598-020-69293-4 |
PMID: | 32704071 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2045-2322 |
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DOI: | 10.1038/s41598-020-69293-4 |