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发育中的中枢神经系统与对铂类化合物的易感性。

Developing central nervous system and vulnerability to platinum compounds.

作者信息

Bernocchi G, Bottone M G, Piccolini V M, Dal Bo V, Santin G, De Pascali S A, Migoni D, Fanizzi F P

机构信息

Laboratorio di Biologia Cellulare e Neurobiologia, Dipartimento di Biologia Animale, Università di Pavia, Via Ferrata 1, 27100 Pavia, Italy.

出版信息

Chemother Res Pract. 2011;2011:315418. doi: 10.1155/2011/315418. Epub 2011 Feb 15.

DOI:10.1155/2011/315418
PMID:22312552
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3265252/
Abstract

Comparative studies on the effects of the platinum complexes in use or in clinical trials are carried out in order to discover differences in the neurotoxic potential and the reversibility of neurotoxicity. In this paper, we summarized the current literature on neurotoxicity and chemoresistance of cisplatin (cisPt) and discussed our recent efforts on the interference of cisPt and a new platinum compound [Pt(O,O'-acac)(γ-acac)(DMS)] (PtAcacDMS), with high specific reactivity with sulphur ligands instead of nucleobases as cisPt, on some crucial events of rat postnatal cerebellum development. The acute effects of drug treatments on cell proliferation and death in the external granular layer and granule cell migration and the late effects on the dendrite growth of Purkinje cells were evaluated. Together with the demonstrated antineoplastic effectiveness in vitro, compared with cisPt, data suggest a lower neurotoxicity of PtAcacDMS, in spite of its presence in the brain that involves considerations on the blood brain barrier permeability.

摘要

为了发现铂配合物在使用中或临床试验中的神经毒性潜力及神经毒性可逆性的差异，人们开展了相关对比研究。在本文中，我们总结了关于顺铂（cisPt）神经毒性和化学抗性的现有文献，并讨论了我们最近在研究cisPt和一种新的铂化合物[Pt(O,O'-acac)(γ-acac)(DMS)]（PtAcacDMS）对大鼠出生后小脑发育的一些关键事件的干扰方面所做的工作。PtAcacDMS与硫配体具有高特异性反应性，而不像cisPt那样与核碱基反应。我们评估了药物处理对颗粒细胞外颗粒层细胞增殖和死亡、颗粒细胞迁移的急性影响，以及对浦肯野细胞树突生长的后期影响。与cisPt相比，尽管PtAcacDMS存在于大脑中这涉及到血脑屏障通透性的问题，但体外实验数据表明其抗肿瘤有效性的同时，也显示出较低的神经毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a5/3265252/bcea28b4a1b1/CHRP2011-315418.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a5/3265252/4cd34b0d598d/CHRP2011-315418.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a5/3265252/1ff14e1d54f4/CHRP2011-315418.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a5/3265252/cb1a5ab57b37/CHRP2011-315418.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a5/3265252/bcea28b4a1b1/CHRP2011-315418.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a5/3265252/4cd34b0d598d/CHRP2011-315418.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a5/3265252/1ff14e1d54f4/CHRP2011-315418.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a5/3265252/cb1a5ab57b37/CHRP2011-315418.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67a5/3265252/bcea28b4a1b1/CHRP2011-315418.004.jpg

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