Neuroprotective Role of Selected Antioxidant Agents in Preventing Cisplatin-Induced Damage of Human Neurons In Vitro

Jelena Popović, Andrijana Klajn, Tatjana Paunesku, Qing Ma, Si Chen, Barry Lai, Milena Stevanović*, Gayle E. Woloschak

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect of platinum-based chemotherapy and decreases the quality of life of cancer patients. We compared neuroprotective properties of several agents using an in vitro model of terminally differentiated human cells NT2-N derived from cell line NT2/D1. Sodium azide and an active metabolite of amifostine (WR1065) increase cell viability in simultaneous treatment with cisplatin. In addition, WR1065 protects the non-dividing neurons by decreasing cisplatin caused oxidative stress and apoptosis. Accumulation of Pt in cisplatin-treated cells was heterogeneous, but the frequency and concentration of Pt in cells were lowered in the presence of WR1065 as shown by X-ray fluorescence microscopy (XFM). Transition metals accumulation accompanied Pt increase in cells; this effect was equally diminished in the presence of WR1065. To analyze possible chemical modulation of Pt-DNA bonds, we examined the platinum L III near edge spectrum by X-ray absorption spectroscopy. The spectrum found in cisplatin-DNA samples is altered differently by the addition of either WR1065 or sodium azide. Importantly, a similar change in Pt edge spectra was noted in cells treated with cisplatin and WR1065. Therefore, amifostine should be reconsidered as a candidate for treatments that reduce or prevent CIPN.

Original languageEnglish (US)
JournalCellular and molecular neurobiology
DOIs
StatePublished - Jan 1 2019

Keywords

  • Amifostine
  • CIPN
  • Cisplatin
  • Neuroprotection
  • XFM

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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