Sumatriptan alleviates radiation-induced oral mucositis in rats by inhibition of NF-kB and ERK activation, prevention of TNF-α and ROS release. (November 2020)

• Record Type: Journal Article
• Authors: Ala, Moein; Mohammad Jafari, Razieh; Ala, Mahan; Agbele, Alaba Tolulope; Hejazi, Sedigheh Marjaneh; Tavangar, Seyed Mohammad; Mahdavi, Seyed Rabi Mehdi; Dehpour, Ahmad Reza
• Is Part Of: Archives of oral biology. Volume 119(2020)
• Publication Date: 2020-11
• Subjects: Sumatriptan -- Radiation-induced oral mucositis -- Inflammation -- Apoptosis -- NF-kB -- p-ERK -- TNF-α -- Stress oxidative -- TUNEL -- Rat; Mouth -- Periodicals; Mouth -- Diseases -- Periodicals; Dentistry -- Periodicals; Electronic journals; 617.6005
• DOI: 10.1016/j.archoralbio.2020.104919
• Languages: English
• ISSNs: 0003-9969

Abstract

Graphical abstract: Highlights: Low-dose sumatriptan has shown an anti-inflammatory and anti-apoptotic profile in radiation-induced oral mucositis. Sumatriptan restricted both NF-kβ expression and activation in irradiated tissue. Sumatriptan prevent the release of TNF-α pro-inflammatory cytokine. Sumatriptan dose-dependently decreased p-ERK and diminished its effect on the spread of inflammation and apoptosis. Low-dose sumatriptan could reduce MDA level. Abstract: Objectives: Oral mucositis caused by radiation therapy is a common problem in cancer patients, especially those with head and neck cancer. Numerous experimental and clinical studies have attempted to find a drug to alleviate oral mucositis. Sumatriptan, is conventionally used to treat migraine attack and cluster headache. Recently, low doses have been shown to have anti-inflammatory properties. In this study we aimed to measure the effect of sumatriptan on experimental radiotherapy-induced oral mucositis. Material and Methods: This study evaluates the use of sumatriptan 0.3 and 1 mg/kg in radiation-induced oral mucositis. In order to induce oral mucositis, six rats from each group received 8-Gy of X-ray in a single session. Likewise, three rats from each group received 26-Gy of X-ray. The latter dose of X-ray was used for inducing severe mucositis and apoptosis evaluation by TUNEL assay, while the first dose was used for histopathological and molecular assessments. On 8th day after irradiation, specimens were collected from their tongues for histology, TUNEL and molecular assessments. Results: Radiation caused mucosal atrophy, derangement of the tissue and vasodilation. Sumatriptan significantly decreased histopathological score and alleviated mucosal atrophy. As well, there was no evidence of vasodilation in the sumatriptan group. Likewise, sumatriptan decreased the increased level of NF-kB and prevented its activation as well as ERK phosphorylation. In addition, Sumatriptan-treated rats had lower tissue level of TNF-α, reactive oxygen species and fewer apoptotic cells in TUNEL assay. Conclusion: Based on study results, sumatriptan mitigate radiation-induced oral mucositis by inhibiting NF-kB, ERK and limiting the release of TNF-α, oxidative stress factor and apoptosis.