Sildenafil Improves Radiation-Induced Oral Mucositis by Attenuating Oxidative Stress, Nf-Κb, Erk and Jnk Signalling Pathways Publisher Pubmed



Ala M^{1, 2} ; Mohammad Jafari R¹ ; Ala M^{1, 2} ; Hejazi SM^{4, 5} ; Tavangar SM^{6, 7} ; Mahdavi SR^{8, 9} ; Dehpour AR^{1, 2} Show Affiliations
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.