The Role of Ionic Homeostasis in Cisplatin-Induced Neurotoxicity: A Preliminary Study

Abstract

Objective: 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 antineoplasticagent that causes neuronal excitotoxicity. According to some studies, calcium influx increases, whereas potassiumefflux decreases neuronal death. Nimodipine and glibenclamide were used to analyze the role of ionicflows in CDDP-induced neurotoxicity in rat primary cerebellar granule cell (CGC) culture.Materials and Methods: 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 intoculture. Neurotoxicity was investigated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide, a tetrazole) assay. One-way analysis of variance, Kruskal–Wallis H test, and Tukey test were appliedfor statistical analysis.Results: CDDP induced neurotoxicity in a concentration-dependent manner. Neither nimodipine nor glibenclamidewas able to protect CGCs against CDDP neurotoxicity.Conclusion: By blocking L-type voltage-gated calcium channels, nimodipine did not prevent CDDP neurotoxicityin CGCs. Ca2+ influx via these channels seemed to be insufficient to cause a change in CDDPinducedneurotoxicity. Similarly, glibenclamide failed to prevent CDDP neurotoxicity. Further studies areneeded to elucidate the mechanisms of these preliminary results.