Liba Benjamin, Naples James, Bezyk Elizabeth, Campbell Charlene, Mei Michael, Parham Kourosh
*University of Connecticut School of Medicine †Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, UConn Health, Farmington, Connecticut.
Otol Neurotol. 2017 Dec;38(10):e501-e505. doi: 10.1097/MAO.0000000000001616.
There are temporal changes in the outer-hair-cell-specific protein, prestin, in the blood after administration of low-dose cisplatin.
Two rodent models of ototoxicity were used. After control and baseline data collection, mice (n = 30) and guinea pigs (n = 10), respectively, were treated with cisplatin at 8 mg/kg. Auditory brainstem responses were recorded on Days 1, 3, 7, and 14 after treatment. Five mice were sacrificed at each time point and serum samples were obtained. A group of 10 guinea pigs were tested and serum samples were collected at each time point. Serum prestin concentrations were measured using separate enzyme-linked immunosorbent assays for each species.
Auditory brainstem responses thresholds changed relatively little in mice, but gradually increased in guinea pigs, as a function of time after cisplatin exposure. In contrast, serum prestin concentrations rose, reaching a peak on Days 3 and 7 after cisplatin treatment in mouse and guinea pig, respectively, before declining back to or below baseline/control levels 14 days after treatment.
There was a time-dependent pattern of change in serum prestin after exposure to low-dose cisplatin in a resistant (mouse) and sensitive (guinea pig) rodent models. These comparative results suggest prestin may serve as a biomarker for cisplatin ototoxicity.
给予低剂量顺铂后,血液中外毛细胞特异性蛋白——预应力蛋白(prestin)会发生时间性变化。
使用两种耳毒性啮齿动物模型。在收集对照和基线数据后,分别对小鼠(n = 30)和豚鼠(n = 10)给予8mg/kg的顺铂。在治疗后的第1、3、7和14天记录听觉脑干反应。每个时间点处死5只小鼠并获取血清样本。对一组10只豚鼠进行测试,并在每个时间点收集血清样本。使用针对每个物种的单独酶联免疫吸附测定法测量血清预应力蛋白浓度。
顺铂暴露后,小鼠的听觉脑干反应阈值变化相对较小,而豚鼠的听觉脑干反应阈值随时间逐渐升高。相比之下,血清预应力蛋白浓度升高,在小鼠和豚鼠中分别于顺铂治疗后的第3天和第7天达到峰值,然后在治疗14天后下降回到或低于基线/对照水平。
在抗性(小鼠)和敏感(豚鼠)啮齿动物模型中,暴露于低剂量顺铂后血清预应力蛋白存在时间依赖性变化模式。这些比较结果表明,预应力蛋白可能作为顺铂耳毒性的生物标志物。