Department of Otolaryngology and Communicative Sciences, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.
Department of Otolaryngology and Communicative Sciences, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA; School of Medicine, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.
Hear Res. 2021 May;404:108202. doi: 10.1016/j.heares.2021.108202. Epub 2021 Feb 12.
The guinea pig is a commonly-used animal model in hearing research, as their audible frequency range is similar to that of humans, and they possess comparatively large cochleae among rodents. Numerous studies have investigated the ototoxic effects of cisplatin in guinea pigs, but these have been mostly limited to single high-dose bolus injections of cisplatin. This method of drug administration is not consistent with human treatment schedules, and therefore lacks translational value to clinical applications. We tested several different cisplatin dosing schedules in guinea pigs based on common research based and clinical regimens, measuring the resulting hearing loss and morbidity (weight loss). We propose a dosing paradigm of once-weekly 4 mg/kg cisplatin injections for three weeks to best mimic clinical treatment schedules. This method resulted in a configuration of hearing loss similar to what is observed in humans along with minimal changes in weight.
豚鼠是听力研究中常用的动物模型，因为它们的可听频率范围与人类相似，而且在啮齿动物中它们具有相对较大的耳蜗。许多研究已经调查了顺铂在豚鼠中的耳毒性作用，但这些研究大多仅限于单次大剂量顺铂冲击注射。这种给药方法与人类治疗方案不一致，因此对临床应用缺乏转化价值。我们根据常见的研究和临床方案，在豚鼠中测试了几种不同的顺铂给药方案，测量了由此产生的听力损失和发病率（体重减轻）。我们提出了每周一次 4mg/kg 顺铂注射三次的给药方案，以最好地模拟临床治疗方案。这种方法导致的听力损失模式与人类观察到的相似，而体重变化最小。
