Shin Seung-Heon, Ye Mi-Kyung, Chae Mi-Hyun, Geum Sang-Yen, Aboraia Ahmed S, Abdel-Aal Abu-Baker M, Qayed Wesam S, El-Wahab Hend A A Abd, Abou-Ghadir Ola F, Aboul-Fadl Tarek
Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Daegu Catholic University, Daegu 42472, Republic of Korea.
Department of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.
Biomedicines. 2024 Aug 29;12(9):1965. doi: 10.3390/biomedicines12091965.
Allergic rhinitis (AR) is a common chronic disease that significantly impacts the quality of life. Lidocaine is known to have anti-inflammatory and immunomodulatory effects. This study evaluated the effect of lidocaine analogs in a (DP)-induced AR mouse model. An AR model was developed using BALB/c mice via intraperitoneal sensitization with DP and intranasal challenge with DP. One hour before stimulation with DP, lidocaine analogs, EI137 and EI341 (at a dose of 0.5 or 5 ug/g), were administered intranasally. Nasal symptoms and serum total IgE, interleukin (IL)-4, IL-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α levels were evaluated. Reverse-transcription polymerase chain reaction was used to determine IL-4, IL-10, and IFN-γ, as well as the expression of their mRNA transcription factors in the sinonasal mucosa. Histologic changes were evaluated using hematoxylin and eosin and periodic acid-Schiff staining. The DP-induced AR mouse model had increased serum levels of total IgE and cytokines. EI137 and EI341 significantly suppressed the levels of total IgE, IL-4, and TNF-α. Intranasal instillation of EI137 and EI341 significantly inhibited IL-4, IL-10, and IFN-γ mRNA expression, as well as inflammatory cells and mucus-producing goblet cells. Lidocaine analogs also suppressed DP-stimulated IL-4, IFN-γ, and IFN-γ production by splenocytes. Intranasal instillation of EI137 and EI341 exhibited anti-allergic and anti-inflammatory effects, influenced by Th1 and Th2 inflammatory cytokines. These lidocaine analogs suppressed DP-induced sinonasal mucosal inflammation, inflammatory cell infiltration, and mucus hypersecretion.
变应性鼻炎（AR）是一种常见的慢性疾病，会显著影响生活质量。利多卡因已知具有抗炎和免疫调节作用。本研究评估了利多卡因类似物在二磷酸腺苷（ADP）诱导的AR小鼠模型中的作用。通过用ADP进行腹腔致敏和用ADP进行鼻内激发，使用BALB/c小鼠建立AR模型。在用ADP刺激前1小时，通过鼻内给予利多卡因类似物EI137和EI341（剂量为0.5或5μg/g）。评估鼻症状以及血清总IgE、白细胞介素（IL）-4、IL-10、干扰素（IFN）-γ和肿瘤坏死因子（TNF）-α水平。采用逆转录聚合酶链反应来测定IL-4、IL-10和IFN-γ及其mRNA转录因子在鼻窦黏膜中的表达。使用苏木精和伊红以及过碘酸希夫染色评估组织学变化。ADP诱导的AR小鼠模型血清中总IgE和细胞因子水平升高。EI137和EI341显著抑制总IgE、IL-4和TNF-α水平。鼻内滴注EI137和EI341显著抑制IL-4、IL-10和IFN-γ mRNA表达，以及炎性细胞和产生黏液的杯状细胞。利多卡因类似物还抑制ADP刺激的脾细胞产生IL-4、IFN-γ和IFN-γ。鼻内滴注EI137和EI341表现出抗过敏和抗炎作用，受Th1和Th2炎性细胞因子影响。这些利多卡因类似物抑制了ADP诱导的鼻窦黏膜炎症、炎性细胞浸润和黏液分泌过多。
