%0 Journal Article
%T Oxaliplatin neurotoxicity ¨C no general ion channel surface-charge effect
%A Amir Broomand
%A Elin Jerremalm
%A Jeffrey Yachnin
%A Hans Ehrsson
%A Fredrik Elinder
%J Journal of Negative Results in BioMedicine
%D 2009
%I BioMed Central
%R 10.1186/1477-5751-8-2
%X To our surprise, we did not see any effects on the current amplitudes, on the current time courses, or on the voltage dependence of the Shaker wild-type channel. Oxaliplatin is expected to bind to cysteines. Therefore, we explored if there could be a specific effect on single (E418C) and double-cysteine (R362C/F416C) mutated Shaker channels previously shown to be sensitive to cysteine-specific reagents. Neither of these channels were affected by oxaliplatin. The clear lack of effect on the Shaker K channel suggests that oxaliplatin or its monochloro complex has no general surface-charge effect on the channels, as has been suggested before, but rather a specific effect to the channels previously shown to be affected.The platinum-based chemotherapeutic drug oxaliplatin has been used in the clinic for about ten years. The therapeutic indication is metastatic colorectal cancer. The mechanism of action is not fully understood, but it is assumed that DNA-adduct formation is one route to cell destruction [1]. The dose-limiting side effect of oxaliplatin treatment is neurotoxicity. A unique and unpleasant acute neurosensory toxicity with paresthesias and dysesthesias of the distal extremities and perioral region occurs shortly after infusion in as much as 90% of the patients. These symptoms can be worsened or triggered by cold, but are reversed within hours or days after treatment. After cumulative doses of about 800 mg/m2 another form of neurotoxicity, with paresthesias and dysesthesias persisting between cycles and problems with sensorimotor coordination is seen in about 10¨C15% of the patients. Most of the patients recover a few months after treatment discontinuation [2,3]. Many patients who receive a clinical benefit from oxaliplatin cannot continue treatment because of worsening neurotoxicity. Our understanding of the mechanism underlying this is limited and research in this area could lead to prolonged treatment with this useful drug.Oxaliplatin has a half-life of abou
%U http://www.jnrbm.com/content/8/1/2