title: Electron microscopy in rat brain slices reveals rapid accumulation of Cisplatin on ribosomes and other cellular components only in glia.
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 (atomic mass = 195). 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.
authors.affiliation: Department of Neuroscience, Universidad Central del Caribe, Bayamón, PR 00960, USA.
authors.forename: Lidia
authors.initials: L
authors.lastname: Zueva
authors.affiliation: Department of Physiology, Universidad Central del Caribe, Bayamón, PR 00960, USA.
authors.forename: Yomarie
authors.initials: Y
authors.lastname: Rivera
authors.affiliation: Department of Biochemistry, Universidad Central del Caribe, Bayamón, PR 00960, USA.
authors.forename: Lilia
authors.initials: L
authors.lastname: Kucheryavykh
authors.affiliation: Department of Physiology, Universidad Central del Caribe, Bayamón, PR 00960, USA ; Department of Biochemistry, Universidad Central del Caribe, Bayamón, PR 00960, USA.
authors.forename: Serguei N
authors.initials: SN
authors.lastname: Skatchkov
authors.affiliation: Department of Biochemistry, Universidad Central del Caribe, Bayamón, PR 00960, USA.
authors.forename: Misty J
authors.initials: MJ
authors.lastname: Eaton
authors.affiliation: Department of Physiology, Universidad Central del Caribe, Bayamón, PR 00960, USA.
authors.forename: Priscila
authors.initials: P
authors.lastname: Sanabria
authors.affiliation: Department of Physiology, Universidad Central del Caribe, Bayamón, PR 00960, USA.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Inyushin