The potential role of amlodipine on experimentally induced bacterial rhinosinusitis

Abstract Introduction: Antibiotics are frequently used for the treatment of rhinosinusitis. Concerns have been raised regarding the adverse effects of antibiotics and growing resistance. The lack of development of new antibiotic compounds has increased the necessity for exploration of non-antibiotic compounds that have antibacterial activity. Amlodipine is a non-antibiotic compound with anti-inflammatory activity. Objective: In this study we aimed to investigate the potential role of amlodipine in the treatment of rhinosinusitis by evaluating its effects on tissue oxidative status, mucosal histology and inflammation. Methods: Fifteen adult albino guinea pigs were inoculated with Staphylococcus aureus and treated with saline, cefazolin sodium, or amlodipine for 7 days. The control group was composed by five healthy guinea pigs. Animals were sacrificed after the treatment. Histopathological changes were identified using Hematoxylin-Eosin staining. Inflammation was assessed by Polymorphonuclear Leukocyte infiltration density. Tissue levels of antioxidants (superoxide dismutase, glutathione) and an oxidative product (malondialdehyde) were determined. Results: In rhinosinusitis induced animals, amlodipine reduced loss of cilia, lamina propria edema and collagen deposition compared to placebo (saline) and although not superior to cefazolin, amlodipine decreased polymorphonuclear leukocyte infiltration. The superoxide dismutase activity and glutathione levels were reduced, whereas the malondialdehyde levels were increased significantly in all three-treatment groups compared to the control group. Amlodipine treated group showed significantly increased superoxide dismutase and glutathione levels and decreased malondialdehyde levels compared to all treatment groups. Conclusion: The non-antibiotic compound amlodipine may have a role in acute rhinosinusitis treatment through tissue protective, antioxidant and anti-inflammatory mechanisms.

摘要
引言：抗生素常被用于鼻窦炎（rhinosinusitis）的临床治疗。当前，抗生素的不良反应与日益严峻的细菌耐药性问题已引发学界广泛关注。新型抗生素化合物研发的停滞不前，使得探索具备抗菌活性的非抗生素类化合物的需求愈发迫切。氨氯地平（amlodipine）是一种具有抗炎活性的非抗生素类化合物。

研究目的：本研究旨在通过评估氨氯地平对鼻窦组织氧化状态、黏膜组织学特征及炎症反应的影响，探究其在鼻窦炎治疗中的潜在作用。

研究方法：将15只成年白化豚鼠接种金黄色葡萄球菌（Staphylococcus aureus）以构建鼻窦炎模型，随后分为三组分别给予生理盐水、头孢唑林钠（cefazolin sodium）或氨氯地平治疗，持续7天；另设5只健康豚鼠作为对照组。治疗周期结束后处死所有实验动物。采用苏木精-伊红（Hematoxylin-Eosin）染色法观察组织病理变化，以多形核白细胞（Polymorphonuclear Leukocyte）浸润密度评估炎症程度，并检测组织内抗氧化物质——超氧化物歧化酶（superoxide dismutase）、谷胱甘肽（glutathione）——及氧化产物丙二醛（malondialdehyde）的水平。

研究结果：相较于生理盐水安慰剂组，造模鼻窦炎的豚鼠经氨氯地平治疗后，其鼻窦黏膜纤毛丢失、固有层水肿及胶原沉积的病理损伤均得到显著改善；尽管氨氯地平的疗效未优于头孢唑林钠，但其可有效降低鼻窦组织的多形核白细胞浸润程度。与健康对照组相比，三个给药组的超氧化物歧化酶活性与谷胱甘肽水平均有所下降，而丙二醛水平则显著升高。相较于其余两个给药组，氨氯地平治疗组的超氧化物歧化酶与谷胱甘肽水平显著升高，丙二醛水平显著降低。

研究结论：非抗生素类化合物氨氯地平可通过组织保护、抗氧化及抗炎多重机制，在急性鼻窦炎的治疗中发挥潜在应用价值。