Adenosine amine congener ameliorates cisplatin-induced hearing loss

作     者：Niliksha Gunewardene Cindy X Guo Ann CY Wong Peter R Thorne Srdjan M Vlajkovic 

作者机构：Department of Physiology the University of Auckland Auckland 1010New Zealand Department of Otolaryngology the University of Melbourne Melbourne Parkville VIC 3010 Australia Translational Neuroscience Facility School of Medical Sciences University of New South Wales Sydney NSW 2052 Australia Department of Physiology Section of Audiology and Centre for Brain ResearchFaculty of Medical and Health Sciences the University of AucklandAuckland 1010 New Zealand 

出 版 物：《World Journal of Otorhinolaryngology》 (世界耳鼻咽喉科杂志)

年 卷 期：2013年第3卷第3期

页      面：100-107页

学科分类：1002[医学-临床医学] 100213[医学-耳鼻咽喉科学] 10[医学] 

基　　金：Supported by Action on Hearing Loss(United Kingdom) 

主　　题：Cisplatin Cochlea Ototoxicity Hearing loss Adenosine receptors Adenosine amine congener Otoprotection 

摘      要：AIM: To investigate a novel pharmacological intervention to mitigate cisplatin ototoxicity using a selective adenosine A1 receptor agonist adenosine amine congener(ADAC).METHODS: Male Wistar rats(8-10 wk) were exposed to a two-cycle cisplatin treatment similar to clinical course of cancer chemotherapy. Each cycle comprised 4 d of intraperitoneal cisplatin injections(1 mg/kg twice daily) separated by 10 d of rest. ADAC(100 μg/kg) or drug vehicle solution(control) was administered intraperitoneally for 5 d at 24 h intervals during the second cisplatin cycle(Regime 1), or upon completion of the cisplatin treatment(Regime 2). Hearing thresholds were measured using auditory brainstem responses(ABR) before cisplatin administration(baseline) and 7 d after the end of cisplatin treatment. Histological analysis of cochlear tissues included hair cell counting and qualitative assessment of apoptosis using terminal deoxynucleotidyl transferase mediated d UTP nick end labelling(TUNEL) ***: ABR threshold shifts in cisplatin-treated Wistar rats ranged from 5-29 d B across the frequency range used in the study(4-24 k Hz). Higher frequencies(16-24 k Hz) were mostly affected by cisplatin ototoxicity(mean threshold shift 25-29 d B). ADAC treatment during the second cisplatin cycle reduced cisplatininduced threshold shifts by 12-16 d B(P 0.01) at higher frequencies compared to control vehicle-treated rats. However, the treatment was ineffective if ADAC administration was delayed until after the completion of the cisplatin regime. Functional recovery was supported by increased survival of hair cells in the cochlea. Qualitative analysis using TUNEL staining demonstrated reduced apoptosis of the outer hair cells and marginal cells in the stria vascularis in animals treated with ADAC during the second cisplatin ***: A1 adenosine receptor agonist ADAC mitigates cisplatin-induced cochlear injury and hearing loss, however its potential interference with antineoplast