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The Anti-Diabetic Drug Metformin Protects against Chemotherapy-Induced Peripheral Neuropathy in a Mouse Model
Chemotherapy-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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4067328/ https://www.ncbi.nlm.nih.gov/pubmed/24955774 http://dx.doi.org/10.1371/journal.pone.0100701 |
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author | Mao-Ying, Qi-Liang Kavelaars, Annemieke Krukowski, Karen Huo, Xiao-Jiao Zhou, Wenjun Price, Theodore J. Cleeland, Charles Heijnen, Cobi J. |
author_facet | Mao-Ying, Qi-Liang Kavelaars, Annemieke Krukowski, Karen Huo, Xiao-Jiao Zhou, Wenjun Price, Theodore J. Cleeland, Charles Heijnen, Cobi J. |
author_sort | Mao-Ying, Qi-Liang |
collection | PubMed |
description | Chemotherapy-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. |
format | Online Article Text |
id | pubmed-4067328 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-40673282014-06-25 The Anti-Diabetic Drug Metformin Protects against Chemotherapy-Induced Peripheral Neuropathy in a Mouse Model Mao-Ying, Qi-Liang Kavelaars, Annemieke Krukowski, Karen Huo, Xiao-Jiao Zhou, Wenjun Price, Theodore J. Cleeland, Charles Heijnen, Cobi J. PLoS One Research Article Chemotherapy-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. Public Library of Science 2014-06-23 /pmc/articles/PMC4067328/ /pubmed/24955774 http://dx.doi.org/10.1371/journal.pone.0100701 Text en © 2014 Mao-Ying et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Mao-Ying, Qi-Liang Kavelaars, Annemieke Krukowski, Karen Huo, Xiao-Jiao Zhou, Wenjun Price, Theodore J. Cleeland, Charles Heijnen, Cobi J. The Anti-Diabetic Drug Metformin Protects against Chemotherapy-Induced Peripheral Neuropathy in a Mouse Model |
title | The Anti-Diabetic Drug Metformin Protects against Chemotherapy-Induced Peripheral Neuropathy in a Mouse Model |
title_full | The Anti-Diabetic Drug Metformin Protects against Chemotherapy-Induced Peripheral Neuropathy in a Mouse Model |
title_fullStr | The Anti-Diabetic Drug Metformin Protects against Chemotherapy-Induced Peripheral Neuropathy in a Mouse Model |
title_full_unstemmed | The Anti-Diabetic Drug Metformin Protects against Chemotherapy-Induced Peripheral Neuropathy in a Mouse Model |
title_short | The Anti-Diabetic Drug Metformin Protects against Chemotherapy-Induced Peripheral Neuropathy in a Mouse Model |
title_sort | anti-diabetic drug metformin protects against chemotherapy-induced peripheral neuropathy in a mouse model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4067328/ https://www.ncbi.nlm.nih.gov/pubmed/24955774 http://dx.doi.org/10.1371/journal.pone.0100701 |
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