Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Sildenafil Improves Radiation-Induced Oral Mucositis by Attenuating Oxidative Stress, Nf-Κb, Erk and Jnk Signalling Pathways Publisher Pubmed



Ala M1, 2 ; Mohammad Jafari R1 ; Ala M1, 2 ; Hejazi SM4, 5 ; Tavangar SM6, 7 ; Mahdavi SR8, 9 ; Dehpour AR1, 2
Authors
Show Affiliations
Authors Affiliations
  1. 1. Experimental Medicine Research Center, School of medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Faculty of Dentistry, Golestan University of Medical Sciences, Gorgan, Iran
  4. 4. Medical Physics and Biomedical Engineering Department, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Advanced Medical Technologies and Equipment Institute Research Center for Molecular and Cellular in Imaging, Bio-optical Imaging Group, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Pathology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Chronic Diseases Research Center, Endocrinology and Metabolism Population Science Institute, Tehran University of Medical Sciences, Iran
  8. 8. Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran
  9. 9. Department of Medical Physics, School of medicine, Iran University of Medical Sciences, Tehran, Iran

Source: Journal of Cellular and Molecular Medicine Published:2022


Abstract

Radiation-induced oral mucositis is a common and dose-limiting complication of head and neck radiotherapy with no effective treatment. Previous studies revealed that sildenafil, a phosphodiesterase 5 inhibitor, has anti-inflammatory and anti-cancer effects. In this study, we investigated the effect of sildenafil on radiation-induced mucositis in rats. Two doses of radiation (8 and 26 Gy X-ray) were used to induce low-grade and high-grade oral mucositis, separately. A control group and three groups of sildenafil citrate-treated rats (5, 10, and 40 mg/kg/day) were used for each dose of radiation. Radiation increased MDA and activated NF-κB, ERK and JNK signalling pathways. Sildenafil significantly decreased MDA level, nitric oxide (NO) level, IL1β, IL6 and TNF-α. The most effective dose of sildenafil was 40 mg/kg/day in this study. Sildenafil also significantly inhibited NF-κB, ERK and JNK signalling pathways and increased bcl2/bax ratio. In addition, high-dose radiation severely destructed the mucosal layer in histopathology and led to mucosal cell apoptosis in the TUNEL assay. Sildenafil significantly improved mucosal structure and decreased inflammatory cell infiltration after exposure to high-dose radiation and reduced apoptosis in the TUNEL assay. These findings show that sildenafil can improve radiation-induced oral mucositis and decrease the apoptosis of mucosal cells via attenuation of inflammation and oxidative stress. © 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.