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Topical Esomeprazole Mitigates Radiation-Induced Dermal Inflammation and Fibrosis.

Authors
  • Pham, Ngoc1
  • Ludwig, Michelle S1
  • Wang, Min1
  • Ebrahimpour, Afshin1
  • Bonnen, Mark D1
  • Diwan, Abdul Hafeez2
  • Kim, Soo Jung3
  • Bryan, Jason4
  • Newton, Jared M5, 6
  • Sikora, Andrew G5
  • Donovan, Donald T5
  • Sandulache, Vlad5
  • Ghebre, Yohannes T1, 7
  • 1 Departments of Radiation Oncology.
  • 2 Departments of Pathology and Immunology.
  • 3 Departments of Dermatology.
  • 4 Departments of Smith Radiation Oncology Clinic, Harris Health System, Houston, Texas 77030.
  • 5 Departments of Otolaryngology - Head and Neck Surgery.
  • 6 Departments of Interdepartmental Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, Texas 77030.
  • 7 Departments of Medicine, Section on Pulmonary and Critical Care Medicine.
Type
Published Article
Journal
Radiation Research
Publisher
BioOne (Radiation Research Society)
Publication Date
Nov 01, 2019
Volume
192
Issue
5
Pages
473–482
Identifiers
DOI: 10.1667/RR15398.1
PMID: 31415221
Source
Medline
Language
English
License
Unknown

Abstract

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.

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