Department of Otolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, 421 Curie Blvd., BRB 1212, Philadelphia, PA, 19104, USA.
Department of Pharmacology, Southern Illinois University School of Medicine, 801 N. Rutledge St, Springfield, IL, 62702, USA.
Sci Rep. 2022 Oct 27;12(1):18032. doi: 10.1038/s41598-022-23034-x.
A mouse model with cisplatin-induced ototoxicity was used in addition to human samples from the ITMAT Biobank at the University of Pennsylvania. Mouse auditory brainstem responses (ABR), inner ear histology, perilymph cisplatin sampling, and measurement of serum prestin via ELISA were performed. Human serum prestin level was measured via ELISA in patients with otological issues after cisplatin treatment and compared to matched controls. Serum prestin was significantly elevated before ABR threshold shifts in mice exposed to cisplatin compared to control mice. Prestin concentration also correlated with the severity of hearing threshold shifts in mice. After an extended rest post-cisplatin treatment, prestin returned to baseline levels in mice and humans. Prestin was significantly elevated in the serum before the onset of objective hearing loss and correlated with the severity of hearing damage indicating that prestin may function as an effective biomarker of cisplatin-induced ototoxicity. Human serum prestin levels responded similarly to mice > 3 weeks from ototoxic exposure with decreased levels of prestin in the serum.
此外,还使用了顺铂诱导耳毒性的小鼠模型以及宾夕法尼亚大学 ITMAT 生物银行的人类样本。进行了小鼠听觉脑干反应(ABR)、内耳组织学、外淋巴液顺铂取样以及 ELISA 测量血清 prestin。在接受顺铂治疗后出现耳科问题的患者中,通过 ELISA 测量了人血清 prestin 水平,并与匹配的对照组进行了比较。与对照组相比,暴露于顺铂的小鼠在 ABR 阈值改变之前血清 prestin 水平显著升高。 prestin 浓度也与小鼠听力阈值改变的严重程度相关。在顺铂治疗后延长的休息期后,小鼠和人类的 prestin 恢复到基线水平。在客观听力损失发生之前,血清中的 prestin 水平显著升高,并与听力损伤的严重程度相关,表明 prestin 可能作为顺铂诱导耳毒性的有效生物标志物。人类血清 prestin 水平与小鼠相似,在耳毒性暴露 3 周以上时,血清 prestin 水平降低。