Tanyeli Talip Talha, Karadaş Hatice, Akyıldız İlker, Gökdoğan Ozan, Sönmez Çiğdem, Çavuş Mehmet Emin, Kaptan Zeynep, Uzunkulaoğlu Hakkı, Arslan Necmi, Zeybek Naciye Dilara
Clinic of Otorhinolaryngology, Head and Neck Surgery, Ankara Polatli State Hospital, Ankara, Turkey.
Department of Otorhinolaryngology, Head and Neck Surgery, Ankara Training and Research Hospital, Ankara, Turkey.
J Int Adv Otol. 2019 Aug;15(2):237-246. doi: 10.5152/iao.2019.6208.
The aim of our study was to investigate the effects of folic acid on cisplatin-induced ototoxicity.
Thirty Wistar albino rats were divided into five groups. Group I received intraperitoneal cisplatin (IP) 10 mg/kg/day and IP folic acid 10 mg/kg/day; Group II received IP cisplatin 10 mg/kg/day and IP physiological saline; Group III received IP cisplatin 10 mg/kg/day and intratympanic (IT) folic acid 0.15 mL/day; Group IV received IP cisplatin 10 mg/kg/day and IT physiological saline; and Group V received IT folic acid 0.15 mL/day. Before and after drug administration, plasma homocysteine, folic acid levels, and auditory brainstem evoked responses (ABR) were measured. The rats were then sacrificed, and the inner ears were processed for electron microscopy.
The differences of ABR thresholds in Group I compared to Group II were significantly smaller at 4 kHz, 8 kHz, and 16 kHz, whereas they were smaller but not statistically significant at 12 kHz in ABR. The differences of ABR thresholds in Group III compared to Group IV were significantly smaller at 12 kHz, and smaller but not statistically significant at 4 kHz, 8 kHz, and 16 kHz. Cisplatin treatment resulted in the degeneration of the cells of the organ of Corti, stria vascularis, and spiral ganglion. The cells of the organ of Corti, stria vascularis, and spiral ganglion showed a partially preserved morphology in both Group I and Group III.
Our study results suggests that folic acid is a potential agent in preventing cisplatin-induced ototoxicity.
本研究旨在探讨叶酸对顺铂所致耳毒性的影响。
30只Wistar白化大鼠分为五组。第一组腹腔注射顺铂10mg/kg/天及腹腔注射叶酸10mg/kg/天；第二组腹腔注射顺铂10mg/kg/天及腹腔注射生理盐水；第三组腹腔注射顺铂10mg/kg/天及鼓室内注射叶酸0.15mL/天；第四组腹腔注射顺铂10mg/kg/天及鼓室内注射生理盐水；第五组鼓室内注射叶酸0.15mL/天。给药前后测量血浆同型半胱氨酸、叶酸水平及听性脑干反应（ABR）。然后处死大鼠，取内耳进行电子显微镜检查。
第一组与第二组相比，在4kHz、8kHz和16kHz时ABR阈值差异明显较小，而在12kHz时ABR阈值差异较小但无统计学意义。第三组与第四组相比，在12kHz时ABR阈值差异明显较小，在4kHz、8kHz和16kHz时差异较小但无统计学意义。顺铂治疗导致柯蒂氏器、血管纹和螺旋神经节细胞变性。第一组和第三组中柯蒂氏器、血管纹和螺旋神经节细胞的形态均有部分保留。
我们的研究结果表明，叶酸是预防顺铂所致耳毒性的一种潜在药物。
