Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan; Department of Pharmacy Practice, Tri-Service General Hospital, Taipei, Taiwan.
Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan.
Toxicol Appl Pharmacol. 2019 Sep 1;378:114604. doi: 10.1016/j.taap.2019.114604. Epub 2019 May 30.
This study investigated the protective effects of dextromethorphan (DXM) on noise-induced hearing loss (NIHL) in rats. This study aimed to improve the auditory threshold and to understand the protective effects of DXM against N-methyl-d-aspartate (NMDA)-induced neurite degeneration of serotonergic neurons. The animals were exposed to 8-kHz narrowband noise at a 118-dB sound pressure level for 3.5 h. The hearing thresholds were determined by measuring the auditory brainstem response to click stimuli. Serotonin transporter (SERT) expression was determined through micro-positron emission tomography (PET) using N,N-dimethyl-2-(2-amino-4-F-fluorophenylthio)benzylamine (4-[F]-ADAM). We also investigated the effects of DXM on NMDA-induced morphological changes in the primary cultures of rat serotonergic neurons. NIHL significantly improved after prophylactic treatment with DXM (p < .05). SERT density in DXM-treated rats was significantly higher than that in non-DXM-treated rats. Because prophylactic medication restored the NMDA-inhibited neurite length of serotonergic neurons and presented SERT density, DXM could be a potential agent in alleviating NIHL.
本研究旨在探讨右美沙芬(DXM)对噪声诱导听力损失(NIHL)的保护作用。该研究旨在提高听觉阈值,并了解 DXM 对 N-甲基-D-天冬氨酸(NMDA)诱导的 5-羟色胺能神经元突起退化的保护作用。动物在 118 分贝声压级的 8 千赫兹窄带噪声中暴露 3.5 小时。通过测量听觉脑干反应对点击刺激的反应来确定听力阈值。通过使用 N,N-二甲基-2-(2-氨基-4-F-氟苯硫基)苯甲胺(4-[F]-ADAM)的微正电子发射断层扫描(PET)来确定 5-羟色胺转运体(SERT)的表达。我们还研究了 DXM 对 NMDA 诱导的大鼠 5-羟色胺能神经元原代培养物形态变化的影响。预防性给予 DXM 后,NIHL 显著改善(p<0.05)。DXM 治疗组大鼠的 SERT 密度明显高于非 DXM 治疗组大鼠。由于预防性药物恢复了 NMDA 抑制的 5-羟色胺能神经元的突起长度并呈现 SERT 密度,因此 DXM 可能是缓解 NIHL 的潜在药物。