JN Ad Instruments
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Neurophysiol 85: 2293-2297, 2001;
0022-3077/01 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (72)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Grolleau, F.
Right arrow Articles by Gamelin, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Grolleau, F.
Right arrow Articles by Gamelin, E.

The Journal of Neurophysiology Vol. 85 No. 5 May 2001, pp. 2293-2297
Copyright ©2001 by the American Physiological Society

RAPID COMMUNICATION

A Possible Explanation for a Neurotoxic Effect of the Anticancer Agent Oxaliplatin on Neuronal Voltage-Gated Sodium Channels

Françoise Grolleau,1 Laurence Gamelin,2 Michèle Boisdron-Celle,2 Bruno Lapied,1 Marcel Pelhate,1 and Erick Gamelin2

 1Laboratoire de Neurophysiologie Unité Propre de Recherche de l'Enseignement Supérieur Equipe d'Accueil (UPRES EA) 2647, Université d'Angers, Unité de Formation et de Recherche (UFR) Sciences, F-49045 Angers Cedex; and  2Laboratoire de Biologie Moléculaire, Immunologie et Thérapeutique des Cancers (BMITC), Centre Paul Papin, Centre Hospitalier Universitaire d'Angers, F-49033 Angers Cedex, France

Grolleau, Françoise, Laurence Gamelin, Michèle Boisdron-Celle, Bruno Lapied, Marcel Pelhate, and Erick Gamelin. A Possible Explanation for a Neurotoxic Effect of the Anticancer Agent Oxaliplatin on Neuronal Voltage-Gated Sodium Channels. J. Neurophysiol. 85: 2293-2297, 2001. Oxaliplatin, a new widely used anticancer drug, displays frequent, sometimes severe, acute sensory neurotoxicity accompanied by neuromuscular signs that look like the symptoms observed in tetany and myotonia. The whole cell patch-clamp technique was employed to investigate the oxaliplatin effects on the electrophysiological properties of short-term cultured dorsal unpaired median (DUM) neurons isolated from the CNS of the cockroach Periplaneta americana. Within the clinical concentration range, oxaliplatin (40-500 µM), applied intracellularly, decreased the amplitude of the voltage-gated sodium current resulting in a reduction of half the amplitude of the action potential. For comparison, two other platinum derivatives, cisplatin and carboplatin, were found to be ineffective at reducing the sodium current amplitude. In addition, we compared the oxaliplatin action to those of its metabolites dichloro-diaminocyclohexane platinum (dach-Cl2-platin) and oxalate. Oxalate (500 µM) was found to be effective, like oxaliplatin, at reducing the inward sodium current amplitude, whereas dach-Cl2-platin (500 µM) failed to change the current amplitude. Interestingly, the effect of oxalate or oxaliplatin could be mimicked by using intracellularly applied 10 mM bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA), known as chelator of calcium ions. We concluded that oxaliplatin was capable of altering the voltage-gated sodium channels through a pathway involving calcium ions probably immobilized by its metabolite oxalate. The medical interest of preventing acute neurotoxic side effects of oxaliplatin by infusing Ca2+ and Mg2+ is discussed.




This article has been cited by other articles:


Home page
 BrainHome page
S. B. Park, C. S.-Y. Lin, A. V. Krishnan, D. Goldstein, M. L. Friedlander, and M. C. Kiernan
Oxaliplatin-induced neurotoxicity: changes in axonal excitability precede development of neuropathy
Brain, October 1, 2009; 132(10): 2712 - 2723.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
S. B. Park, D. Goldstein, C. S.-Y. Lin, A. V. Krishnan, M. L. Friedlander, and M. C. Kiernan
Acute Abnormalities of Sensory Nerve Function Associated With Oxaliplatin-Induced Neurotoxicity
J. Clin. Oncol., March 10, 2009; 27(8): 1243 - 1249.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
L. Gamelin, M. Boisdron-Celle, A. Morel, A. L. Poirier, V. Berger, E. Gamelin, C. Tournigand, and A. de Gramont
Oxaliplatin-Related Neurotoxicity: Interest of Calcium-Magnesium Infusion and No Impact on Its Efficacy
J. Clin. Oncol., March 1, 2008; 26(7): 1188 - 1189.
[Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
L. Gamelin, O. Capitain, A. Morel, A. Dumont, S. Traore, L. B. Anne, S. Gilles, M. Boisdron-Celle, and E. Gamelin
Predictive Factors of Oxaliplatin Neurotoxicity: The Involvement of the Oxalate Outcome Pathway
Clin. Cancer Res., November 1, 2007; 13(21): 6359 - 6368.
[Abstract] [Full Text] [PDF]

Home page
 Am J Health Syst PharmHome page
P. Andre, S. Cisternino, A.-L. Roy, F. Chiadmi, J. Schlatter, P. Agranat, O. Fain, and J.-E. Fontan
Stability of oxaliplatin in infusion bags containing 5% dextrose injection
Am. J. Health Syst. Pharm., September 15, 2007; 64(18): 1950 - 1954.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
S. L. Spunt, B. B. Freeman III, C. A. Billups, V. McPherson, R. B. Khan, C. B. Pratt, and C. F. Stewart
Phase I Clinical Trial of Oxaliplatin in Children and Adolescents With Refractory Solid Tumors
J. Clin. Oncol., June 1, 2007; 25(16): 2274 - 2280.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
W.-S. Wang, J.-K. Lin, T.-C. Lin, W.-S. Chen, J.-K. Jiang, H.-S. Wang, T.-J. Chiou, J.-H. Liu, C.-C. Yen, and P.-M. Chen
Oral Glutamine Is Effective for Preventing Oxaliplatin-Induced Neuropathy in Colorectal Cancer Patients
Oncologist, March 1, 2007; 12(3): 312 - 319.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
A. A. Argyriou, E. Chroni, P. Polychronopoulos, G. Iconomou, A. Koutras, T. Makatsoris, M. K. Gerolymos, P. Gourzis, K. Assimakopoulos, and H. P. Kalofonos
Efficacy of oxcarbazepine for prophylaxis against cumulative oxaliplatin-induced neuropathy
Neurology, December 26, 2006; 67(12): 2253 - 2255.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
A. V. Krishnan, D. Goldstein, M. Friedlander, and M. C. Kiernan
Oxaliplatin and Axonal Na+ Channel Function In vivo
Clin. Cancer Res., August 1, 2006; 12(15): 4481 - 4484.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
T. Lecomte, B. Landi, P. Beaune, P. Laurent-Puig, and M.-A. Loriot
Glutathione S-Transferase P1 Polymorphism (Ile105Val) Predicts Cumulative Neuropathy in Patients Receiving Oxaliplatin-Based Chemotherapy.
Clin. Cancer Res., May 15, 2006; 12(10): 3050 - 3056.
[Abstract] [Full Text] [PDF]

Home page
 The Annals of PharmacotherapyHome page
R. J Cersosimo
Oxaliplatin-Associated Neuropathy: A Review
Ann. Pharmacother., January 1, 2005; 39(1): 128 - 135.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
D. Hagrman, J. Goodisman, and A.-K. Souid
Kinetic Study on the Reactions of Platinum Drugs with Glutathione
J. Pharmacol. Exp. Ther., February 1, 2004; 308(2): 658 - 666.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurophysiol.Home page
S. Dugravot, F. Grolleau, D. Macherel, A. Rochetaing, B. Hue, M. Stankiewicz, J. Huignard, and B. Lapied
Dimethyl Disulfide Exerts Insecticidal Neurotoxicity Through Mitochondrial Dysfunction and Activation of Insect KATP Channels
J Neurophysiol, July 1, 2003; 90(1): 259 - 270.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online