Neurotoxic Effects of Platinum Compounds: Studies in vivo on Intracellular Calcium Homeostasis in the Immature Central Nervous System

Toxics

Graziella Bernocchi²  Francesco P. Fanizzi¹  Sandra A. De Pascali¹  Valeria M. Piccolini²  Caterina Gasperini²  Violetta Insolia²  Maria Grazia Bottone²  Guido Cavaletti³ 

[1] Dipartimento di Scienze e Tecnologie Biologiche e Ambientali (Di.S.Te.B.A.), Università del Salento, via provinciale Lecce-Monteroni centro Ecotekne, 73100 Lecce, Italy; E-Mails:;Dipartimento di Biologia e Biotecnologie “L. Spallanzani” Università di Pavia, via Ferrata 9, 27100 Pavia, Italy; E-Mails:Dipartimento di Biologia e Biotecnologie “L. Spallanzani” Università di Pavia, via Ferrata 9, 27100 Pavia, Italy;

关键词: platinum compounds;    neurotoxicity;    CNS development;    calcium homeostasis systems;    purkinje neurons;    dentate granule cells;   

DOI  :  10.3390/toxics3020224

来源: mdpi

【 摘 要 】

Platinum compounds cause significant clinical neurotoxicity. Several studies highlight neurological complications especially in paediatric oncology patients with Central Nervous System (CNS) and non-CNS malignancies. To understand the toxicity mechanisms of platinum drugs at cellular and molecular levels in the immature brain, which appears more vulnerable to injury than in the adult one, we compared the effects in vivo of the most used platinum compounds, i.e., cisdichlorodiammineplatinum (cisplatin, cisPt), and the new [Pt(O,O′-acac)(γ-acac)(DMS)] (PtAcacDMS). As models of developing brain areas, we have chosen the cerebellum and hippocampus dentate gyrus. Both areas show the neurogenesis events, from proliferation to differentiation and synaptogenesis, and therefore allow comparing the action of platinum compounds with DNA and non-DNA targets. Here, we focused on the changes in the intracellular calcium homeostasis within CNS architecture, using two immunohistochemical markers, the calcium buffer protein Calbindin and Plasma Membrane Calcium ATPase. From the comparison of the cisPt and PtAcacDMS effects, it emerges how essential the equilibrium and synergy between CB and PMCA1 is or how important the presence of at least one of them is to warrant the morphology and function of nervous tissue and limit neuroarchitecture damages, depending on the peculiar and intrinsic properties of the developing CNS areas.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.