Clinic of Otorhinolaryngology, Head and Neck Surgery, Bakırköy Research and Training Hospital, Istanbul, Turkey.
Eur Arch Otorhinolaryngol. 2012 Jan;269(1):45-52. doi: 10.1007/s00405-011-1582-2. Epub 2011 Mar 27.
The aim of this study was to investigate the effectiveness of the oral administration of pomegranate extract (PE) as a protective agent against cisplatin-induced ototoxicity. The study included a prospective, controlled animal study Group 1 (n = 6), received no cisplatin or PE, and group 2 (n = 6) received cisplatin at 8 mg/kg/day for 3 consecutive days. Group 3 (n = 6) received not only cisplatin at 8 mg/kg/day for 3 consecutive days, but also received PE (100 μL/day) via gavage for 5 days prior to the cisplatin injection and for 3 days concomitantly with the cisplatin injections. To measure cisplatin ototoxic effects, "distortion product otoacoustic emissions" (DPOAE) were analyzed 3 days before and after the cisplatin injections. Histological changes in the cochleas were observed by light microscopy. Compared with group 3, the DPOAE amplitudes of group 2 decreased significantly. Among the groups, there was a statistically significant difference in basal and mid turn external ciliated cells (ECC) number, but there was no statistically significant difference in apical turn. Differences in stria vascularis (SV) changes were statistically significant between the groups, and the median score for SV injury was significantly greater in group 2 than in group 3. Differences in the median scores for SGC changes being significantly greater in group 2 than in group 3. In conclusion, these results indicated that oral administration of PE afforded statistically significant protection to the cochlea in rats from cisplatin toxicity, and thus, oral experimental dose of PE administration may have a protective effect against cisplatin ototoxicity in rats.
本研究旨在探讨口服石榴提取物 (PE) 作为顺铂诱导耳毒性保护剂的有效性。该研究包括一项前瞻性、对照动物研究,第 1 组(n = 6)未接受顺铂或 PE 治疗,第 2 组(n = 6)连续 3 天每天接受 8mg/kg 的顺铂治疗,第 3 组(n = 6)不仅连续 3 天每天接受 8mg/kg 的顺铂治疗,而且在顺铂注射前 5 天和同时注射顺铂的 3 天内通过灌胃给予 100μL/天的 PE。为了测量顺铂的耳毒性作用,在顺铂注射前 3 天和后 3 天分析“畸变产物耳声发射”(DPOAE)。通过光镜观察耳蜗的组织学变化。与第 3 组相比,第 2 组的 DPOAE 振幅明显降低。各组之间,基底和中部外毛细胞(ECC)数量有统计学差异,但顶部无统计学差异。各组之间血管纹(SV)变化有统计学差异,第 2 组的 SV 损伤中位数评分明显高于第 3 组。各组之间听神经节细胞(SGC)变化的中位数评分差异有统计学意义,第 2 组明显大于第 3 组。总之,这些结果表明,口服 PE 可使大鼠耳蜗对顺铂毒性具有统计学显著的保护作用,因此,口服实验剂量的 PE 给药可能对大鼠的顺铂耳毒性具有保护作用。