Carozzi Valentina, Chiorazzi Alessia, Canta Annalisa, Oggioni Norberto, Gilardini Alessandra, Rodriguez-Menendez Virginia, Avezza Federica, Crippa Luca, Ceresa Cecilia, Nicolini Gabriella, Bossi Mario, Cavaletti Guido
Department of Neuroscience and Biomedical Technologies, University of Milan Bicocca, Via Cadore 48, 20052 Monza (MI), Italy.
Eur J Cancer. 2009 Mar;45(4):656-65. doi: 10.1016/j.ejca.2008.10.038. Epub 2008 Dec 16.
We have characterised for the first time the general and neurological side effects experienced when using a series of chronic non-lethal cisplatin + paclitaxel schedules in Wistar rats, selected according to our previous experience and the animals' maximum tolerated dose. At the pathological level, the use of combination schedules was definitely more toxic at the kidney and sternal bone marrow level than the single-agent schedules. At the neurophysiological examination based on the assessment of the nerve conduction velocity measurement in the tail nerve, we identified only one combination schedule that was more neurotoxic than the similar schedules based on single-agent administration. This observation was confirmed by the neuropathological examination performed on the sciatic nerve, dorsal root ganglia, ventral and dorsal roots. Our study supports the hypothesis that the general and, to a lesser extent, neurological effects of a combination of cisplatin and paclitaxel are different from those of the administration of both drugs as single agents. We believe that these models may be useful for testing neuroprotective strategies.
我们首次对根据我们之前的经验和动物最大耐受剂量选择的一系列慢性非致死性顺铂+紫杉醇给药方案在Wistar大鼠中使用时所经历的一般和神经副作用进行了表征。在病理水平上，联合给药方案在肾脏和胸骨骨髓水平上的毒性肯定比单药给药方案更大。在基于尾神经神经传导速度测量评估的神经生理学检查中，我们仅确定了一种联合给药方案比基于单药给药的类似方案具有更高的神经毒性。对坐骨神经、背根神经节、腹根和背根进行的神经病理学检查证实了这一观察结果。我们的研究支持这样一种假设，即顺铂和紫杉醇联合使用的一般影响以及在较小程度上的神经影响与两种药物单独给药的影响不同。我们认为这些模型可能有助于测试神经保护策略。
