Table of Contents
Chemotherapy Research and Practice
Volume 2014, Article ID 174039, 5 pages
http://dx.doi.org/10.1155/2014/174039
Research Article

Electron Microscopy in Rat Brain Slices Reveals Rapid Accumulation of Cisplatin on Ribosomes and Other Cellular Components Only in Glia

1Department of Neuroscience, Universidad Central del Caribe, Bayamón, PR 00960, USA
2Department of Physiology, Universidad Central del Caribe, Bayamón, PR 00960, USA
3Department of Biochemistry, Universidad Central del Caribe, Bayamón, PR 00960, USA

Received 23 September 2014; Accepted 16 December 2014; Published 28 December 2014

Academic Editor: H. J. Schmoll

Copyright © 2014 Lidia Zueva et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Cisplatin is a widely used, effective anticancer drug. Its use, however, is associated with several side effects including nephrotoxicity and neurotoxicity. It is known that cisplatin is accumulated in cells by the organic cation transport system and reacts with nucleotides, damaging them, but the precise target of cisplatin-induced neurotoxicity remains obscure. Here we report direct visualization of cisplatin inside brain cells using in vivo “cisplatin staining,” a technique that takes advantage of the high electron density of cisplatin, which contains platinum (). After applying 0.1% cisplatin to living brain slices for 30 min, we fixed the tissue and observed the accumulated cisplatin using electron microscopy. We found that cisplatin was localized mainly to ribosomes associated with endoplasmic reticulum (EPR) in glial cells and to the myelin sheath formed by oligodendrocytes around neuronal axons. Staining of nuclear DNA was moderate. Our in vivo “cisplatin staining” method validated that the main target of cisplatin is a direct attack on myelin and the RNA contained in ribosomes.