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舒马曲坦通过抑制 NF-κB 和 ERK 的激活、预防 TNF-α 和 ROS 的释放来缓解大鼠放射性口腔黏膜炎。

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

机构信息

Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, 13145-784, Tehran, Iran.

Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Arch Oral Biol. 2020 Nov;119:104919. doi: 10.1016/j.archoralbio.2020.104919. Epub 2020 Sep 16.

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.

摘要

目的

放疗引起的口腔黏膜炎是癌症患者,尤其是头颈部癌症患者的常见问题。许多实验和临床研究都试图寻找一种药物来缓解口腔黏膜炎。舒马曲坦通常用于治疗偏头痛发作和丛集性头痛。最近,低剂量已显示出抗炎特性。在这项研究中,我们旨在测量舒马曲坦对实验性放疗引起的口腔黏膜炎的影响。

材料和方法

本研究评估了舒马曲坦 0.3 和 1mg/kg 在放射诱导的口腔黏膜炎中的应用。为了诱导口腔黏膜炎,每组 6 只大鼠接受单次 8Gy X 射线照射。同样,每组 3 只大鼠接受 26Gy X 射线照射。后者剂量的 X 射线用于通过 TUNEL 测定法评估严重黏膜炎和细胞凋亡,而前者剂量用于进行组织学和分子评估。照射后第 8 天,从舌部采集标本进行组织学、TUNEL 和分子评估。

结果

放射导致黏膜萎缩、组织紊乱和血管扩张。舒马曲坦显著降低组织学评分并缓解黏膜萎缩。此外,舒马曲坦组未见血管扩张。同样,舒马曲坦降低了 NF-κB 的升高水平,并防止其激活和 ERK 磷酸化。此外,舒马曲坦治疗的大鼠在 TUNEL 测定中具有较低的 TNF-α、活性氧物质水平和较少的凋亡细胞。

结论

根据研究结果,舒马曲坦通过抑制 NF-κB、ERK 并限制 TNF-α、氧化应激因子和凋亡的释放,减轻放疗引起的口腔黏膜炎。

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