The Anti-Diabetic Drug Metformin Protects Against Chemotherapy-Induced Peripheral Neuropathy in a Mouse Model

Simple item page
dc.contributor.authorMao-Ying, Qien_US
dc.contributor.authorKavelaars, Annemiekeen_US
dc.contributor.authorKrukowski, Karenen_US
dc.contributor.authorHuo, Xiao-Jiaoen_US
dc.contributor.authorZhou, Wenjunen_US
dc.contributor.authorPrice, Theodore J.en_US
dc.contributor.authorCleeland, Charlesen_US
dc.contributor.authorHeijnen, Cobi J.en_US
dc.date.accessioned2014-10-07T22:19:26Z
dc.date.available2014-10-07T22:19:26Z
dc.date.created2014-06-23
dc.description.abstractChemotherapy-induced peripheral neuropathy (CIPN) characterized by loss of sensory sensitivity and pain in hands and feet is the major dose-limiting toxicity of many chemotherapeutics. At present, there are no FDA-approved treatments for CIPN. The anti-diabetic drug metformin is the most widely used prescription drug in the world and improves glycemic control in diabetes patients. There is some evidence that metformin enhances the efficacy of cancer treatment. The aim of this study was to test the hypothesis that metformin protects against chemotherapy-induced neuropathic pain and sensory deficits. Mice were treated with cisplatin together with metformin or saline. Cisplatin induced increased sensitivity to mechanical stimulation (mechanical allodynia) as measured using the von Frey test. Co-administration of metformin almost completely prevented the cisplatin-induced mechanical allodynia. Co-administration of metformin also prevented paclitaxel-induced mechanical allodynia. The capacity of the mice to detect an adhesive patch on their hind paw was used as a novel indicator of chemotherapy-induced sensory deficits. Co-administration of metformin prevented the cisplatin-induced increase in latency to detect the adhesive patch indicating that metformin prevents sensory deficits as well. Moreover, metformin prevented the reduction in density of intra-epidermal nerve fibers (IENFs) in the paw that develops as a result of cisplatin treatment. We conclude that metformin protects against pain and loss of tactile function in a mouse model of CIPN. The finding that metformin reduces loss of peripheral nerve endings indicates that mechanism underlying the beneficial effects of metformin includes a neuroprotective activity. Because metformin is widely used for treatment of type II diabetes, has a broad safety profile, and is currently being tested as an adjuvant drug in cancer treatment, clinical translation of these findings could be rapidly achieved. ;en_US
dc.description.sponsorshipUS National Institutes of Health (PO1 CA124787; RO1 NS073939; RO1 NS74999; RO1 NS065926; RO1 GM102575)en_US
dc.identifier.bibliographicCitationMao-Ying, Qi, Annemieke Kavelaars, Karen Krukowski, Xiao-Jiao Huo, et al. 2014. "The anti-diabetic drug Metformin protects against chemotherapy-induced peripheral neuropathy in a mouse model." PLOS One 9(6): e100701-1 to 8.
dc.identifier.issn1932-6203en_US
dc.identifier.issue6en_US
dc.identifier.startpage100701en_US
dc.identifier.urihttp://hdl.handle.net/10735.1/4098
dc.identifier.volume9en_US
dc.publisherPublic Library of Scienceen_US
dc.relation.urihttp://dx.doi.org/10.1371/journal.pone.0100701en_US
dc.rightsCC BY 4.0 (Attribution)en_US
dc.rights©2014 The Authorsen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.source.journalPLOS Oneen_US
dc.subjectMetforminen_US
dc.subjectCisplatinen_US
dc.subjectMiceen_US
dc.subjectChemotherapyen_US
dc.subjectNeuropathyen_US
dc.titleThe Anti-Diabetic Drug Metformin Protects Against Chemotherapy-Induced Peripheral Neuropathy in a Mouse Modelen_US
dc.typeTexten_US
dc.type.genrearticleen_US

Files

Original bundle

Now showing 1 - 1 of 1
Thumbnail Image
Name:
BBS-FR-TJPrice-271104.60.pdf
Size:
809.71 KB
Format:
Adobe Portable Document Format
Description:
Article
Download

Collections

Price, Theodore J.