Unel Cigdem Cengelli, Erol Kevser
Department of Pharmacology, Eskişehir Osmangazi University School of Medicine, Eskişehir, Turkey.
Eurasian J Med. 2018 Jun;50(2):81-85. doi: 10.5152/eurasianjmed.2018.17233. Epub 2018 Jun 1.
The aim of the present study was to investigate the role of ionic homeostasis in cisplatin (cisdiamminedichloroplatinum (II), CDDP)-induced neurotoxicity. CDDP is a severely neurotoxic antineoplastic agent that causes neuronal excitotoxicity. According to some studies, calcium influx increases, whereas potassium efflux decreases neuronal death. Nimodipine and glibenclamide were used to analyze the role of ionic flows in CDDP-induced neurotoxicity in rat primary cerebellar granule cell (CGC) culture.
CGC culture was prepared from the cerebella of Sprague Dawley 5-day-old pups. The submaximal concentration of CDDP was determined and then given with 1, 10, or 50 µM of drugs into culture. Neurotoxicity was investigated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a tetrazole) assay. One-way analysis of variance, Kruskal-Wallis H test, and Tukey test were applied for statistical analysis.
CDDP induced neurotoxicity in a concentration-dependent manner. Neither nimodipine nor glibenclamide was able to protect CGCs against CDDP neurotoxicity.
By blocking L-type voltage-gated calcium channels, nimodipine did not prevent CDDP neurotoxicity in CGCs. Ca influx via these channels seemed to be insufficient to cause a change in CDDP-induced neurotoxicity. Similarly, glibenclamide failed to prevent CDDP neurotoxicity. Further studies are needed to elucidate the mechanisms of these preliminary results.
本研究旨在探讨离子稳态在顺铂（顺二氯二氨合铂（II），CDDP）诱导的神经毒性中的作用。CDDP是一种具有严重神经毒性的抗肿瘤药物，可导致神经元兴奋性毒性。根据一些研究，钙内流增加，而钾外流减少会导致神经元死亡。使用尼莫地平和格列本脲来分析离子流在大鼠原代小脑颗粒细胞（CGC）培养中CDDP诱导的神经毒性中的作用。
从5日龄Sprague Dawley幼崽的小脑中制备CGC培养物。确定CDDP的亚最大浓度，然后将1、10或50 μM的药物加入培养物中。使用MTT（3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐，一种四氮唑）试验研究神经毒性。采用单因素方差分析、Kruskal-Wallis H检验和Tukey检验进行统计分析。
CDDP以浓度依赖性方式诱导神经毒性。尼莫地平和格列本脲均不能保护CGC免受CDDP神经毒性的影响。
通过阻断L型电压门控钙通道，尼莫地平不能预防CGC中的CDDP神经毒性。通过这些通道的钙内流似乎不足以引起CDDP诱导的神经毒性的变化。同样，格列本脲未能预防CDDP神经毒性。需要进一步研究以阐明这些初步结果的机制。
