Cisplatin and dimethyl sulfoxide react to form an adducted compound with reduced cytotoxicity and neurotoxicity

Stephanie J. Fischer, Linda M. Benson, Abdul Fauq, Stephen Naylor, Anthony John Windebank

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Purpose: We present work that demonstrates that cisplatin reacts rapidly with dimethyl sulfoxide (DMSO) in solution and identify the structure and reactivity of the resulting compound. Methods: Electrospray ionization-mass spectrometry (ESI-MS) and NMR were used to identify the chemical structure of compounds formed when DMSO reacts with cisplatin. We studied the reactivity of the identified compound with DNA. In vitro toxicity studies in neurons and cancer cells and in vivo toxicity studies in rats were used to determine both the cancer chemotherapeutic and toxic effects of the identified compound. Results: Cisplatin binds rapidly with DMSO to form a DMSO adduct. The resulting compound has reduced ability to bind to double-stranded DNA both in vitro and in cells. This compound has reduced toxicity for cancer cells and neurons in vitro. In vivo nephrotoxicity studies show that the adducted compound has different nephrotoxicity and elimination characteristics than cisplatin. Conclusions: From this work, we conclude that dissolving cisplatin in DMSO results in formation of an adducted compound with different therapeutic and biological characteristics. Furthermore, future studies which propose using DMSO in combination with cisplatin for chemotherapeutic treatment in patients must be reconsidered. Due to the rapidity and nature of the reaction, DMSO and cisplatin should not be combined for patient treatment.

Original languageEnglish (US)
Pages (from-to)444-452
Number of pages9
JournalNeuroToxicology
Volume29
Issue number3
DOIs
StatePublished - May 2008

Fingerprint

Cytotoxicity
Dimethyl Sulfoxide
Cisplatin
Toxicity
Neurons
Cells
Patient treatment
Electrospray ionization
Neoplasms
Electrospray Ionization Mass Spectrometry
Poisons
DNA
Mass spectrometry
Rats
Therapeutics
Nuclear magnetic resonance
In Vitro Techniques

Keywords

  • Cisplatin
  • Cytotoxicity
  • DMSO
  • Mass spectroscopy
  • Neurotoxicity

ASJC Scopus subject areas

  • Neuroscience(all)
  • Cellular and Molecular Neuroscience
  • Toxicology

Cite this

Cisplatin and dimethyl sulfoxide react to form an adducted compound with reduced cytotoxicity and neurotoxicity. / Fischer, Stephanie J.; Benson, Linda M.; Fauq, Abdul; Naylor, Stephen; Windebank, Anthony John.

In: NeuroToxicology, Vol. 29, No. 3, 05.2008, p. 444-452.

Research output: Contribution to journalArticle

Fischer, Stephanie J. ; Benson, Linda M. ; Fauq, Abdul ; Naylor, Stephen ; Windebank, Anthony John. / Cisplatin and dimethyl sulfoxide react to form an adducted compound with reduced cytotoxicity and neurotoxicity. In: NeuroToxicology. 2008 ; Vol. 29, No. 3. pp. 444-452.
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