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Effect of noise conditioning on cisplatin-induced ototoxicity: a pilot study

机译:噪声调节对顺铂诱导的耳毒性的影响:一项初步研究

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Background Cisplatin is a platinum-based chemotherapeutic agent that is highly effective in the treatment of cancer. Ototoxicity is an important dose-limiting adverse effect of cisplatin, in addition to nephrotoxicity. Studies have shown that cisplatin-induced ototoxicity is mainly a result of generated reactive oxygen species. Sulfur-containing compounds such as L-N acetylcysteine (L-NAC) and D-methionine (D-MET) have shown promising results as potent otoprotectors against cisplatin-induced ototoxicity in animal studies. Material and Method In this study, we investigated a method to increase the efficacy of L-NAC and D-MET without increasing dose. Sprague Dawley rats were noise conditioned for 15 minutes immediately after intraperitoneal injection of 275 mg/kg L-NAC or 300 mg/kg D-MET. Another set of rats received 275 mg/kg L-NAC or 300 mg/kg D-MET alone, and 1 group underwent noise conditioning alone. All 5 groups were administered 14 mg/kg cisplatin intravenously 1 hour after otoprotector injection or 45 minutes after noise conditioning. Results Otoprotectors and noise conditioning, alone or in combination, were analyzed for their ability to reduce cisplatin-induced ototoxicity. The results indicated that the combination of 275 mg/kg L-NAC and noise conditioning afforded more otoprotection than 275 mg/kg L-NAC alone. In the case of D-MET, 300 mg/kg plus noise conditioning was little better than 300 mg/kg D-MET alone. In addition, we found that noise conditioning alone showed otoprotection against cisplatin-induced ototoxicity. Conclusions The ability of noise conditioning to protect against cisplatin-induced ototoxicity requires additional study.
机译:背景技术顺铂是一种基于铂的化学治疗剂,在治疗癌症方面非常有效。除肾毒性外,耳毒性是顺铂重要的剂量限制性副作用。研究表明,顺铂引起的耳毒性主要是产生的活性氧的结果。在动物研究中,含硫化合物如L-N乙酰半胱氨酸(L-NAC)和D-蛋氨酸(D-MET)已显示出有希望的结果,作为抗顺铂诱导的耳毒性的强力耳保护剂。材料和方法在这项研究中,我们研究了在不增加剂量的情况下增加L-NAC和D-MET疗效的方法。腹腔注射275 mg / kg L-NAC或300 mg / kg D-MET后,立即对Sprague Dawley大鼠进行噪声处理15分钟。另一组大鼠仅接受275 mg / kg的L-NAC或300 mg / kg的D-MET,一组仅接受了噪声调节。在注射otoprotector后1小时或在调理噪音后45分钟,对所有5组进行静脉内14 mg / kg顺铂给药。结果分析了单独或组合使用的耳保护剂和噪音调节剂减少顺铂诱导的耳毒性的能力。结果表明,与单独的275 mg / kg L-NAC相比,结合275 mg / kg L-NAC和噪音调节可提供更多的耳保护。对于D-MET,300 mg / kg加上噪音调节比单独使用300 mg / kg D-MET更好。此外,我们发现单独的噪声调节显示出对顺铂诱导的耳毒性的耳保护。结论噪声调节防止顺铂诱发的耳毒性的能力需要进一步研究。

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