Giese Arnaud P J, Guarnaschelli Jess G, Ward Jonette A, Choo Daniel I, Riazuddin Saima, Ahmed Zubair M
Department of Otorhinolaryngology Head & Neck Surgery, School of Medicine, University of Maryland, Baltimore, Maryland, United States of America.
Department of Radiation Oncology, University of Cincinnati, Ohio, United States of America.
PLoS One. 2015 Nov 23;10(11):e0143606. doi: 10.1371/journal.pone.0143606. eCollection 2015.
Radiotherapy of individuals suffering with head & neck or brain tumors subserve the risk of sensorineural hearing loss. Here, we evaluated the protective effect of Aminothiol PrC-210 (3-(methyl-amino)-2-((methylamino)methyl)propane-1-thiol) on the irradiated inner ear of guinea pigs. An intra-peritoneal or intra-tympanic dose of PrC-210 was administered prior to receiving a dose of gamma radiation (3000 cGy) to each ear. Auditory Brainstem Responses (ABRs) were recorded one week and two weeks after the radiation and compared with the sham animal group. ABR thresholds of guinea pigs that received an intra-peritoneal dose of PrC-210 were significantly better compared to the non-treated, control animals at one week post-radiation. Morphologic analysis of the inner ear revealed significant inflammation and degeneration of the spiral ganglion in the irradiated animals not treated with PrC-210. In contrast, when treated with PrC-210 the radiation effect and injury to the spiral ganglion was significantly alleviated. PrC-210 had no apparent cytotoxic effect in vivo and did not affect the morphology or count of cochlear hair cells. These findings suggest that aminothiol PrC-210 attenuated radiation-induced cochlea damage for at least one week and protected hearing.
对头颈部或脑部肿瘤患者进行放射治疗会带来感音神经性听力损失的风险。在此，我们评估了氨硫醇PrC-210（3-（甲基氨基）-2-（（甲基氨基）甲基）丙烷-1-硫醇）对豚鼠受辐照内耳的保护作用。在每只耳朵接受3000 cGy的伽马辐射剂量之前，给予腹腔内或鼓膜内剂量的PrC-210。在辐射后一周和两周记录听觉脑干反应（ABR），并与假手术动物组进行比较。接受腹腔内剂量PrC-210的豚鼠在辐射后一周时的ABR阈值与未治疗的对照动物相比明显更好。内耳的形态学分析显示，未用PrC-210治疗的受辐照动物的螺旋神经节有明显的炎症和退化。相比之下，用PrC-210治疗时，对螺旋神经节的辐射效应和损伤明显减轻。PrC-210在体内没有明显的细胞毒性作用，也不影响耳蜗毛细胞的形态或数量。这些发现表明，氨硫醇PrC-210至少在一周内减轻了辐射诱导的耳蜗损伤并保护了听力。
