Effects of different schedules of oxaliplatin treatment on the peripheral nervous system of the rat
Effects of different schedules of oxaliplatin treatment on the peripheral nervous system of the rat
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DOI：
10.1016/s0959-8049(01)00300-8
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发表时间：
2001-12-01
影响因子：
8.4
通讯作者：
Etienne, GG
中科院分区：
文献类型：
--
作者：
Cavaletti, G;Tredici, G;Etienne, GG
本研究的目的是确定奥沙利铂给药方案对大鼠外周神经毒性和耳毒性发生的影响。动物接受四种不同方案的奥沙利铂治疗，累积剂量分别为36 mg/kg和48 mg/kg(Ip)。神经病理学检查显示，治疗组大鼠背根神经节(DRG)核仁、核仁和体细胞体积缩小，核仁分离。奥沙利铂治疗后感觉神经传导速度(SNCV)减慢，而听觉通路未受影响。治疗后，肾、背根神经节和坐骨神经中均检出铂。经过5周的随访期，尽管在这些组织中仍可检测到铂，但DRG和坐骨神经的病理改变已恢复。结论如下：奥沙利铂神经毒性的主要靶点是背根节，注射间隔时间越短，周围神经病变程度越重，且与奥沙利铂累积剂量有关；外周神经毒性倾向于可逆性；高累积剂量奥沙利铂也无耳毒性。(C)2001爱思唯尔科学有限公司。保留所有权利。
The aim of this study was to determine the influence of oxaliplatin scheduling on the onset of peripheral neurotoxicity and ototoxicity in a rat model. Animals were treated with four different schedules of oxaliplatin using two cumulative doses (36 and 48 mg/kg intraperitoneally (i.p.)). The neuropathological examination evidenced dorsal root ganglia (DRG) nucleolar, nuclear and somatic size reduction with nucleolar segregation in the treated rats. Sensory nerve conduction velocity (SNCV) was reduced after oxaliplatin treatment, while the auditory pathway was unaffected. After treatment, platinum was detected in the kidney, DRG and sciatic nerve. After a 5-week follow-up period, recovery of the pathological changes in the DRG and sciatic nerves occurred, although platinum was still detectable in these tissues. The following conclusions may be drawn: the main targets of oxaliplatin neurotoxicity were the DRG; the shorter the interval between the injections, the higher the severity of peripheral neuropathy and this was also related to the cumulative oxaliplatin dose; the peripheral neurotoxicity tended to be reversible; ototoxicity was absent even with high cumulative doses of oxaliplatin. (C) 2001 Elsevier Science Ltd. All rights reserved.