Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea.
Department of Otorhinolaryngology-Head and Neck Surgery, Gangneung Asan Hospital, College of Medicine University of Ulsan, Gangneung, Republic of Korea.
Eur J Pharm Sci. 2022 Nov 1;178:106291. doi: 10.1016/j.ejps.2022.106291. Epub 2022 Sep 1.
The safety and efficacy of intratympanic (IT) histamine (HIS) injection as an adjuvant to increase the inner ear penetration of dexamethasone (DEX) was investigated in this study. IT injections of DEX-only, 1% HIS+DEX and 4% HIS+DEX were performed in mice with noise-induced hearing loss. An inflammatory reaction in the middle ear was observed only in the 4% HIS+DEX group although no serious cytotoxic effects on the organ of Corti (OC) were observed at that concentration. Compared with the DEX-only group, the perilymphatic concentration of DEX was approximately two times higher in the 1% HIS+DEX group and approximately five times higher in the 4% HIS+DEX group. The expression of the DEX receptor in the cochlea was significantly increased in the 4%-HIS+DEX group. HIS appeared to induce transient damage the microstructure of the RWM with recovery observed within 3 weeks. The 1 and 4% HIS + DEX groups showed a significant recovery of the OC compared with the control group and they also achieved significantly better hearing restoration at 8 kHz in the DPOAE hearing test (P < .05) when compared to the DEX-only group. IT HIS temporarily disrupts the structure of the RWM and middle ear mucosa and significantly enhances the inner ear penetration of DEX. Therefore, IT HIS injection could be a simple and effective adjuvant therapy to increase perilymph concentration of DEX and achieve OC recovery after cochlear damage.
本研究旨在探讨鼓室内（IT）组胺（HIS）注射作为增强地塞米松（DEX）内耳渗透的佐剂的安全性和有效性。在噪声性听力损失的小鼠中进行了仅 DEX、1% HIS+DEX 和 4% HIS+DEX 的 IT 注射。尽管在该浓度下未观察到对 Corti 器（OC）的严重细胞毒性作用，但仅在 4% HIS+DEX 组中观察到中耳的炎症反应。与仅 DEX 组相比，1% HIS+DEX 组的外淋巴液中 DEX 的浓度约为两倍，而 4% HIS+DEX 组的浓度约为五倍。4%-HIS+DEX 组耳蜗中 DEX 受体的表达明显增加。HIS 似乎会引起 RWM 微观结构的短暂损伤，在 3 周内观察到恢复。与对照组相比，1%和 4% HIS+DEX 组的 OC 恢复明显更好，与仅 DEX 组相比，在 DPOAE 听力测试中，8 kHz 时的听力恢复也明显更好（P<.05）。IT HIS 暂时破坏了 RWM 和中耳黏膜的结构，并显著增强了 DEX 的内耳渗透。因此，IT HIS 注射可能是一种简单有效的辅助治疗方法，可增加外淋巴液中 DEX 的浓度，并在耳蜗损伤后实现 OC 的恢复。
