Lou W H
First Affiliated Hospital, Henan Medical University, Zhengzhou.
Zhonghua Er Bi Yan Hou Ke Za Zhi. 1990 Aug;25(4):208-10, 255.
The effect of sodium thiosulfate (STS) on cisplatin (CDDP)-induced ototoxicity in the guinea pigs was studied by surface preparation, outer hair cell counting, electrocochleographic, light and electron microscopic techniques. Seventy-eight guinea pigs were divided into five groups. Group I received intraperitoneal CDDP (2.5 mg/kg/day) alone: group V as control; the other three groups were given the same doses of CDDP as group I with intramuscular STS (600 mg/kg/day) administered 30 min before (group II) or 30 min (group III) and 6 hr (group IV) after CDDP. The results showed that CDDP produced serious ototoxicity both functionally and histologically when given without STS. The first row of outer hair cells (OHC) in basal turn was first damaged. The inner hair cells (IHC) were more resistant than the OHC. The pattern of destruction is similar to that produced by aminoglycosides. Concomitant use of STS, however, significantly reduced CDDP-induced ototoxicity. Transmission electron microscopy showed the degeneration of mitochondria to be the major and earliest sign of OHC damage induced by CDDP. Our present study documented the good protective efficacy of STS against CDDP cochleotoxicity. STS did not reverse the pathological changes already caused by CDDP. This study provided some experimental evidence for the prevention of CDDP ototoxicity in clinical cancer chemotherapy.
通过表面制备、外毛细胞计数、耳蜗电图、光镜和电镜技术研究了硫代硫酸钠(STS)对顺铂(CDDP)诱导的豚鼠耳毒性的影响。78只豚鼠分为五组。第一组单独腹腔注射CDDP(2.5mg/kg/天):第五组作为对照;其他三组给予与第一组相同剂量的CDDP,同时分别在CDDP给药前30分钟(第二组)、给药后30分钟(第三组)和6小时(第四组)肌肉注射STS(600mg/kg/天)。结果表明,未给予STS时,CDDP在功能和组织学上均产生严重耳毒性。基底转外毛细胞(OHC)的第一排首先受损。内毛细胞(IHC)比OHC更具抗性。破坏模式与氨基糖苷类药物所致相似。然而,同时使用STS可显著降低CDDP诱导的耳毒性。透射电镜显示线粒体变性是CDDP诱导的OHC损伤的主要和最早迹象。我们目前的研究证明了STS对CDDP耳蜗毒性具有良好的保护作用。STS不能逆转已由CDDP引起的病理变化。本研究为临床癌症化疗中预防CDDP耳毒性提供了一些实验依据。