Topical Esomeprazole Mitigates Radiation-Induced Dermal Inflammation and Fibrosis
| Autor: | Soo Jung Kim, Ngoc Minh Pham, Mark D. Bonnen, Donald T. Donovan, Vlad C. Sandulache, Michelle Ludwig, Min Wang, Yohannes T. Ghebre, Abdul Hafeez Diwan, Jared M. Newton, Afshin Ebrahimpour, Andrew G. Sikora, Jason Bryan |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Models Anatomic NF-E2-Related Factor 2 medicine.medical_treatment Administration Topical Biophysics Active Transport Cell Nucleus Anti-Inflammatory Agents Inflammation Human skin Article Esomeprazole Mice Fibrosis In vivo medicine Animals Humans Radiology Nuclear Medicine and imaging Skin Wound Healing Radiation Radiotherapy business.industry Gene Expression Profiling Cancer Membrane Proteins medicine.disease Radiation therapy Heme oxygenase Mice Inbred C57BL Disease Models Animal Cancer research medicine.symptom Radiodermatitis business Heme Oxygenase-1 medicine.drug |
| Zdroj: | Radiat Res |
| ISSN: | 1938-5404 |
| Popis: | Radiation therapy is a mainstream strategy in the treatment of several cancer types that are surgically unresectable. Unfortunately, cancer patients often suffer from unintended consequences of radiotherapy, including the development of skin inflammation (dermatitis), which may progress to fibrosis. These morbid complications often require interruption of radiotherapy and threaten the relapse of underlying cancer. Current treatment options for radiation dermatitis are suboptimal and compel the need to develop safer, more effective therapies. In this study, we assessed the biophysical properties of topically-formulated esomeprazole (here referred to as dermaprazole) and performed proof-of-concept studies to evaluate its efficacy in vitro and in vivo. We found that dermaprazole induced nuclear translocation of erythroid 2-related factor 2 (Nrf2) and significantly upregulated heme oxygenase 1 (HO1) gene and protein expression in a 3D human skin model. Our animal study demonstrated that dermaprazole improved macroscopic appearance of the irradiated skin and accelerated healing of the wounds. Histopathology data corroborated the photographic evidence and confirmed that both prophylactically and therapeutically administered dermaprazole conferred potent anti-inflammatory and antifibrotic effects. Gene expression data showed that dermaprazole downregulated several pro-oxidant, pro-inflammatory and profibrotic genes. In conclusion, topical formulation of the FDA-approved drug esomeprazole is highly effective in attenuating dermal inflammation and fibrosis. |
| Databáze: | OpenAIRE |
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