Intratympanic administration of dexamethasone attenuates radiation induced damage to middle ear mucosa

Abstract Radiotherapy (RTx) is a highly effective treatment for head and neck cancer that can cause concurrent damage to surrounding healthy tissues. In cases of nasopharyngeal carcinoma (NPC), the auditory apparatus is inevitably exposed to radiation fields and sustains considerable damage, resulting in dysfunction. To date, little research has been conducted on the changes induced by RTx in the middle ear and the underlying mechanisms involved. Dexamethasone (DEX) is widely used in clinical practice because of its immunosuppressive and anti-inflammatory properties. The present study investigated the effects and underlying mechanisms of DEX delivered via intratympanic administration on RTx-induced damage to the middle ear and human middle ear epithelial (HMEE) cells. Sprague–Dawley (SD) rats were exposed to fractionated RTx (6.6 Gy/day for 5 days), and middle ear samples were collected at 1 and 4 months. Rats that received RTx presented a significant increase in the thickness of the submucosal layer in the middle ear and disorganization of the ciliated epithelium in the Eustachian tube (ET) mucosa. Importantly, intratympanic administration of DEX 30 min before RTx resulted in a lower degree of damage than that in the control group. Furthermore, DEX pretreatment downregulated the expression of cell death pathway markers in HMEE cells. Our collective results potentially support the use of DEX to reduce radiation-induced damage in the middle ear and may contribute to the development of future studies.