Topical Corticosteroid Pretreatment Mitigates Cellular Damage After Caustic Injury to the Nasal Upper Airway Epithelium

Abstract

Background Topical corticosteroids are currently employed to reduce established airway inflammation; their prophylactic use might help limit cellular damage against harmful stimuli. Objectives To determine the effects of a prophylactic topical application of budesonide (BD) on an in vivo nasal epithelium injury model induced by trichloroacetic acid (TCA). Methods C57Bl/6 mice were exposed to intranasal TCA topical application. Three groups received topical intranasal BD, saline solution, or no intervention prior to a single topical exposure to TCA. Controls were not exposed to TCA. Whole nasal cavity coronal sections were analyzed at 1, 3, and 6 days postinjury at tissue and cellular levels using histopathological analysis, immunofluorescent staining, and fresh tissue RNA microarray analysis. Results Prophylactic topical corticosteroid exposure protected the nasal epithelium from acute damage, maintaining epithelial thickness and cell survival. Six days following TCA exposure, epithelial and cellular changes were less pronounced on the BD-treated group compared to all exposure groups. The microarray analysis was used to evaluate the gene transcripts in all treatment groups. Ciliary tip protein, Sentan, and submucosal protein S100b were identified as potential factors in epithelial airway protection; immunofluorescent staining corroborated their presence and location within the respiratory epithelium. Conclusion Topical corticosteroid treatment to the nasal epithelium can mitigate several of the early deleterious effects of acute epithelial damage in experimental airway injuries caused by TCA. These findings suggest a novel, direct cytoprotective effect of corticosteroids on the nasal epithelium, and the potential of expanding the use of prophylactic periprocedural topical corticosteroids for respiratory epithelial tissues.

Editorial

“…Multiple prior studies have evaluated the utility of systemic corticosteroid presurgical or postsurgical therapy for patients undergoing endoscopic sinus surgery, and presurgical and postsurgical treatment with oral and topical corticosteroids are widely employed as antiinflammatory agents in many rhinologic practices. Huang et al 10 assessed the impact of prophylactic topical budesonide pretreatment of the nasal epithelium prior to trichloroacetic acid injury in a mouse model. Their novel topical mouse nasal epithelium injury model demonstrate that preinjury treatment is associated with significantly less surface and subepithelial edema formation in acute stages of upper airway injury, with a return by day 6 after injury to control animals without injury to the nasal epithelium.…”

Intranasal Morphology Transformation Nanomedicines for Long-Term Intervention of Allergic Rhinitis

“… , Common treatments includes allergen avoidance, drug treatment (antihistamines, decongestants, glucocorticoids, etc. ), specific immunotherapy, and surgical intervention. − Among these applications, nasal administration is especially suitable because of rapid absorption of drugs and low required dosage. , However, nasal drug administration usually suffers from mucosa irritants via direct contact, poor permeability, and short residence time in the nasal cavity, which were not beneficial to eliminate rhinitis symptoms. , Therefore, there are urgent demands to develop effective nasal delivery strategies with augmented antiallergic therapeutic efficacy and reduced side effects.…”

“…13,14 However, nasal drug administration usually suffers from mucosa irritants via direct contact, poor permeability, and short residence time in the nasal cavity, which were not beneficial to eliminate rhinitis symptoms. 15,16 Therefore, there are urgent demands to develop effective nasal delivery strategies with augmented antiallergic therapeutic efficacy and reduced side effects. Utilization of intranasal nanoplatform has provided a meaningful exploration in the treatment of allergic rhinitis for reducing direct irritation to nasal mucosal, enhancing in situ permeation, and protecting drugs from degradation and metabolism.…”