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15 August 2019 Topical Esomeprazole Mitigates Radiation-Induced Dermal Inflammation and Fibrosis
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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.

©2019 by Radiation Research Society. All rights of reproduction in any form reserved.
Ngoc Pham, Michelle S. Ludwig, Min Wang, Afshin Ebrahimpour, Mark D. Bonnen, Abdul Hafeez Diwan, Soo Jung Kim, Jason Bryan, Jared M. Newton, Andrew G. Sikora, Donald T. Donovan, Vlad Sandulache, and Yohannes T. Ghebre "Topical Esomeprazole Mitigates Radiation-Induced Dermal Inflammation and Fibrosis," Radiation Research 192(5), 473-482, (15 August 2019). https://doi.org/10.1667/RR15398.1
Received: 1 April 2019; Accepted: 8 July 2019; Published: 15 August 2019
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