Literature DB >> 18439683

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

Stephanie J Fischer1, Linda M Benson, Abdul Fauq, Stephen Naylor, Anthony J Windebank.   

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.

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Year:  2008        PMID: 18439683     DOI: 10.1016/j.neuro.2008.02.010

Source DB:  PubMed          Journal:  Neurotoxicology        ISSN: 0161-813X            Impact factor:   4.294


  21 in total

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8.  Say no to DMSO: dimethylsulfoxide inactivates cisplatin, carboplatin, and other platinum complexes.

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10.  Cisplatin-induced renal injury is independently mediated by OCT2 and p53.

Authors:  Jason A Sprowl; Cynthia S Lancaster; Navjotsingh Pabla; Edwin Hermann; Ashley M Kosloske; Alice A Gibson; Lie Li; Dorothea Zeeh; Eberhard Schlatter; Laura J Janke; Giuliano Ciarimboli; Alex Sparreboom
Journal:  Clin Cancer Res       Date:  2014-06-10       Impact factor: 12.531

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