Bekmez Bilmez Zekiye Eda, Aydin Sedat, Şanli Arif, Altintoprak Niyazi, Demir Mehmet Gökhan, Atalay Erdoğan Banu, Kösemihal Ebru
Bahçelievler State Hospital, Istanbul, Turkey.
Kartal Dr. Lutfi Kirdar Education and Research Hospital Otolaryngology Department, Kartal, Istanbul, Turkey.
Cancer Chemother Pharmacol. 2016 Apr;77(4):875-9. doi: 10.1007/s00280-016-2978-x. Epub 2016 Feb 11.
Cisplatin is a potent chemotherapeutic drug with serious side effects such as ototoxicity which is characterized by irreversible, bilateral, progressive sensorineural hearing loss. Oxytocin, which is a well-known hormone secreting during pregnancy, has antioxidant and antiinflammatory effect. Our study aims to test and compare the effect of intratympanic (IT) and intraperitoneal (IP) oxytocin on cisplatin ototoxicity with DPOAE.
A total of 24 Wistar albino rats were randomly divided into four groups: Group 1 received 0.1-0.3 ml IT saline + IP saline solutions for 4 days (n = 6), Group 2 received cumulative dose of 20 mg/kg IP cisplatin divided into two equal doses in first and second days of experiment + 0.1-0.3 ml IT saline for 4 days, Group 3 received same dose of cisplatin as Group 2 + 0.1-0.3 ml IT oxytocin for 4 days, and Group 4 received same dose of cisplatin as Groups 2 and 3 + IP oxytocin with dose of 1 mg/kg. DPOAE was performed prior to procedure and at the end of the experiment on day 5.
Group 2 showed severe ototoxic effect of cisplatin according to DPOAE result (p < 0.05). When compared with Group 2, DPOAE amplitude reductions were smaller in Group 3 (3.2, 3.8, 4.5, 6.3 and 7.6 kHz) (p < 0.05) and Group 4 which is statistically significant in 5.4, 6.3 and 7.6 kHz (p < 0.05). When Group 3 and Group 4 were compared, reductions were smaller in 2.7 and 3.2 kHz in Group 3 (p < 0.05).
In this study, we showed the protective effect of IT and IP oxytocin on cisplatin ototoxicity. We suggest oxytocin in cisplatin ototoxicity, especially via IT route even with high-dose cisplatin.
顺铂是一种强效化疗药物，具有严重的副作用，如耳毒性，其特征为不可逆的双侧进行性感音神经性听力损失。催产素是孕期分泌的一种知名激素，具有抗氧化和抗炎作用。我们的研究旨在通过畸变产物耳声发射（DPOAE）测试并比较鼓室内（IT）和腹腔内（IP）注射催产素对顺铂耳毒性的影响。
总共24只Wistar白化大鼠被随机分为四组：第1组在4天内接受0.1 - 0.3毫升鼓室内生理盐水 + 腹腔内生理盐水溶液（n = 6）；第2组在实验的第一天和第二天接受累积剂量为20毫克/千克的腹腔内顺铂，分为两个相等剂量，并在4天内接受0.1 - 0.3毫升鼓室内生理盐水；第3组接受与第2组相同剂量的顺铂，并在4天内接受0.1 - 0.3毫升鼓室内催产素；第4组接受与第2组和第3组相同剂量的顺铂，并腹腔内注射1毫克/千克剂量的催产素。在实验前及实验第5天结束时进行DPOAE检测。
根据DPOAE结果，第2组显示出顺铂的严重耳毒性作用（p < 0.05）。与第2组相比（在3.2、3.8、4.5、6.3和7.6千赫兹频率处），第3组的DPOAE幅值降低较小（p < 0.05），第4组在5.4、6.3和7.6千赫兹频率处有统计学意义的降低（p < 0.05）。当比较第3组和第4组时，第3组在2.7和3.2千赫兹频率处的降低较小（p < 0.05）。
在本研究中，我们显示了鼓室内和腹腔内注射催产素对顺铂耳毒性的保护作用。我们建议在顺铂耳毒性中使用催产素，尤其是通过鼓室内途径，即使是高剂量顺铂时。
