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.