The role of endothelin-1 and endothelin receptor antagonists in allergic rhinitis inflammation: ovalbumin-induced rat model

Rhinology journal Pub Date : 2016-09-01 DOI:10.4193/rhino15.059

A. Tatar, M. Yayla, D. Kose, Z. Halıcı, O. Yoruk, E. Polat

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Abstract

Objective: Desloratadine is a biologically active metabolite of loratadine which is indicated for the treatment of allergic rhinitis. Bosentan is a dual endothelin receptor antagonist used to treatment of pulmonary artery hypertension (PAH). In this study, we aimed to determine the role of endothelins in allergic rhinitis (AR) and the effects of endothelin receptor antagonists in AR rat models through comparison with desloratadine. Methods: In total, 20 adult Sprague-Dawley rats were used in this study. An ovalbumin-induced allergic rhinitis model was formed in three study groups except for the control group. Bosentan (100 mg/kg/day) was given to the bosentan-treated group for 7 days and desloratadine (10 mg/kg/day) was administered to the antihistaminic-treated group for 7 days. Nasal symptom scorings and histopathological examinations of the nasal tissues were carried out. Serum IgE levels and ET-1 and TNF-alpha mRNA expression levels were analysed. Between group comparisons for nasal symptoms, histopathological analysis, and molecular analyses were performed with a one-way ANOVA and Duncans multiple comparison tests. Significance was accepted at p smaller than 0.05. Results: Bosentan inhibited nasal symptom more significantly than desloratadine. The IgE level, ET-1 and TNF-alpha mRNA expression levels statistically increased in the allergic rhinitis group when compared to other groups. Conversely, the bosentan-treatment group showed a significant recovery from the same parameters. The deterioration in histopathological parameters reached the highest levels in the allergic rhinitis group. The histopathological findings were close to those of the control group in the bosentan and antihistaminic-treated group. Conclusions: ET-1 is one of the mediators that impact AR development and ET-1 antagonists can be useful for symptom control and for decreasing allergic inflammation in AR patients.

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内皮素-1和内皮素受体拮抗剂在变应性鼻炎中的作用:卵清蛋白诱导的大鼠模型

目的:地氯雷他定是氯雷他定的生物活性代谢物，用于治疗变应性鼻炎。波生坦是一种双重内皮素受体拮抗剂，用于治疗肺动脉高压(PAH)。在本研究中，我们旨在通过与地氯雷他定的比较，确定内皮素在变应性鼻炎(AR)中的作用以及内皮素受体拮抗剂在AR大鼠模型中的作用。方法:选用成年Sprague-Dawley大鼠20只。除对照组外，其余3组均建立卵清蛋白致变应性鼻炎模型。波生坦治疗组给予波生坦100 mg/kg/d，抗组胺治疗组给予地氯雷他定10 mg/kg/d，治疗7 d。进行鼻症状评分和鼻组织病理检查。分析血清IgE水平、ET-1和tnf - α mRNA表达水平。采用单因素方差分析和邓肯多重比较检验进行组间鼻部症状、组织病理学分析和分子分析的比较。p < 0.05时接受显著性。结果:波生坦对鼻部症状的抑制作用优于地氯雷他定。变应性鼻炎组IgE水平、ET-1及tnf - α mRNA表达水平较其他组有统计学升高。相反，波生坦治疗组从相同的参数显示出显着的恢复。变应性鼻炎组组织病理指标恶化程度最高。波生坦和抗组胺治疗组的组织病理学结果与对照组接近。结论:ET-1是影响AR发展的介质之一，ET-1拮抗剂可用于AR患者的症状控制和减轻变应性炎症。

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Rhinology journal

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