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阿司匹林诱导的暂时性阈移在顺铂相关耳毒性动物模型中的保护作用。

The protective effect of aspirin-induced temporary threshold shift in an animal model of cisplatin-related ototoxicity.

作者信息

Tzelnick Sharon, Mizrachi Aviram, Barkan Neta, Shivatzki Shaked, Yosefof Eyal, Hikri Elad, Attias Joseph, Hilly Ohad

机构信息

Department of Otorhinolaryngology Head and Neck Surgery, Rabin Medical Center, 39 Jabotinsky St, Petah Tikva, Israel.

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

出版信息

J Cancer Res Clin Oncol. 2023 May;149(5):2009-2016. doi: 10.1007/s00432-022-04144-5. Epub 2022 Jul 1.

Abstract

PURPOSE

The purpose of this study was to evaluate whether induction of temporary threshold shift (TTS) with aspirin prior to cisplatin exposure can prevent or minimize cisplatin detrimental effects on hearing.

METHODS

We randomly divided BALB mice into three groups: (1) cisplatin only, (2) aspirin only, and (3) combined aspirin/cisplatin. Cisplatin was administered as a single intraperitoneal injection of 14 mg/kg. Aspirin was administered for three weeks via intraperitoneal injection of 200 mg/kg sodium salicylate, twice daily. Air conduction thresholds were recorded using Auditory Brainstem Responses (ABR). Cochleae were harvested and cochlear hair cells were counted using a scanning electron microscope (SEM).

RESULTS

Aspirin-induced TTS have reached an average of 30.05±16.9 dB after 2 weeks. At 60 days, cisplatin-only treated mice experienced an average threshold shifts of 50.7 dB at 4 kHz, 35.16 dB at 8 kHz, 70 dB at 16 kHz, 53.1 dB at 32 kHz. All threshold shifts were significantly worse than for cisplatin/aspirin treated mice with TTS of 11.85 dB at 4 kHz, 3.58 dB at 8 kHz, 16.58  dB at 16 kHz, 20.41 dB at 32 kHz (p < 0.01). Cochlear cell count with SEM has shown reduction in the number of both inner and outer hair cells in the mid-turn in cisplatin treated mice.

CONCLUSION

Aspirin induced TTS can protect from cisplatin-induced ototoxicity. This beneficial effect was demonstrated by auditory thresholds as well as SEM. Larger pre-clinical and clinical studies are still needed to confirm these findings.

摘要

目的

本研究的目的是评估在顺铂暴露前用阿司匹林诱导暂时性阈移(TTS)是否可以预防或最小化顺铂对听力的有害影响。

方法

我们将BALB小鼠随机分为三组:(1)仅用顺铂组,(2)仅用阿司匹林组,(3)阿司匹林/顺铂联合组。顺铂以14mg/kg的剂量单次腹腔注射给药。阿司匹林通过腹腔注射200mg/kg水杨酸钠,每天两次,给药三周。使用听觉脑干反应(ABR)记录气导阈值。收获耳蜗并使用扫描电子显微镜(SEM)对耳蜗毛细胞进行计数。

结果

阿司匹林诱导的TTS在2周后平均达到30.05±16.9dB。在60天时,仅用顺铂治疗的小鼠在4kHz处平均阈移为50.7dB,在8kHz处为35.16dB,在16kHz处为70dB,在32kHz处为53.1dB。所有阈移均明显比顺铂/阿司匹林治疗的小鼠更差,后者在4kHz处TTS为11.85dB,在8kHz处为3.58dB,在16kHz处为16.58dB,在32kHz处为20.41dB(p<0.01)。SEM耳蜗细胞计数显示,顺铂治疗的小鼠中、转的内毛细胞和外毛细胞数量均减少。

结论

阿司匹林诱导的TTS可保护免受顺铂诱导的耳毒性。听觉阈值和SEM均证明了这种有益效果。仍需要更大规模的临床前和临床研究来证实这些发现。

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