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Exenatide Facilitates Recovery from Oxaliplatin-Induced Peripheral Neuropathy in Rats

BACKGROUND: Oxaliplatin has widely been used as a key drug in the treatment of colorectal cancer; however, it causes peripheral neuropathy. Exenatide, a glucagon-like peptide-1 (GLP-1) agonist, is an incretin mimetic secreted from ileal L cells, which is clinically used to treat type 2 diabetes mell...

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Autores principales: Fujita, Shunsuke, Ushio, Soichiro, Ozawa, Nana, Masuguchi, Ken, Kawashiri, Takehiro, Oishi, Ryozo, Egashira, Nobuaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4633148/
https://www.ncbi.nlm.nih.gov/pubmed/26536615
http://dx.doi.org/10.1371/journal.pone.0141921
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author Fujita, Shunsuke
Ushio, Soichiro
Ozawa, Nana
Masuguchi, Ken
Kawashiri, Takehiro
Oishi, Ryozo
Egashira, Nobuaki
author_facet Fujita, Shunsuke
Ushio, Soichiro
Ozawa, Nana
Masuguchi, Ken
Kawashiri, Takehiro
Oishi, Ryozo
Egashira, Nobuaki
author_sort Fujita, Shunsuke
collection PubMed
description BACKGROUND: Oxaliplatin has widely been used as a key drug in the treatment of colorectal cancer; however, it causes peripheral neuropathy. Exenatide, a glucagon-like peptide-1 (GLP-1) agonist, is an incretin mimetic secreted from ileal L cells, which is clinically used to treat type 2 diabetes mellitus. GLP-1 receptor agonists have been reported to exhibit neuroprotective effects on the central and peripheral nervous systems. In this study, we investigated the effects of exenatide on oxaliplatin-induced neuropathy in rats and cultured cells. METHODS: Oxaliplatin (4 mg/kg) was administered intravenously twice per week for 4 weeks, and mechanical allodynia was evaluated using the von Frey test in rats. Axonal degeneration was assessed by toluidine blue staining of sciatic nerves. RESULTS: Repeated administration of oxaliplatin caused mechanical allodynia from day 14 to 49. Although the co-administration of extended-release exenatide (100 μg/kg) could not inhibit the incidence of oxaliplatin-induced mechanical allodynia, it facilitated recovery from the oxaliplatin-induced neuropathy with reparation of axonal degeneration. Inhibition of neurite outgrowth was evaluated in cultured pheochromocytoma 12 (PC12) cells. Exenatide inhibited oxaliplatin-induced neurite degeneration, but did not affect oxaliplatin-induced cell injury in cultured PC12 cells. Additionally, extended-release exenatide had no effect on the anti-tumor activity of oxaliplatin in cultured murine colon adenocarcinoma 26 (C-26) cells or C-26 cell-implanted mice. CONCLUSION: These results suggest that exenatide may be useful for treating peripheral neuropathy induced by oxaliplatin in colorectal cancer patients with type 2 diabetes.
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spelling pubmed-46331482015-11-13 Exenatide Facilitates Recovery from Oxaliplatin-Induced Peripheral Neuropathy in Rats Fujita, Shunsuke Ushio, Soichiro Ozawa, Nana Masuguchi, Ken Kawashiri, Takehiro Oishi, Ryozo Egashira, Nobuaki PLoS One Research Article BACKGROUND: Oxaliplatin has widely been used as a key drug in the treatment of colorectal cancer; however, it causes peripheral neuropathy. Exenatide, a glucagon-like peptide-1 (GLP-1) agonist, is an incretin mimetic secreted from ileal L cells, which is clinically used to treat type 2 diabetes mellitus. GLP-1 receptor agonists have been reported to exhibit neuroprotective effects on the central and peripheral nervous systems. In this study, we investigated the effects of exenatide on oxaliplatin-induced neuropathy in rats and cultured cells. METHODS: Oxaliplatin (4 mg/kg) was administered intravenously twice per week for 4 weeks, and mechanical allodynia was evaluated using the von Frey test in rats. Axonal degeneration was assessed by toluidine blue staining of sciatic nerves. RESULTS: Repeated administration of oxaliplatin caused mechanical allodynia from day 14 to 49. Although the co-administration of extended-release exenatide (100 μg/kg) could not inhibit the incidence of oxaliplatin-induced mechanical allodynia, it facilitated recovery from the oxaliplatin-induced neuropathy with reparation of axonal degeneration. Inhibition of neurite outgrowth was evaluated in cultured pheochromocytoma 12 (PC12) cells. Exenatide inhibited oxaliplatin-induced neurite degeneration, but did not affect oxaliplatin-induced cell injury in cultured PC12 cells. Additionally, extended-release exenatide had no effect on the anti-tumor activity of oxaliplatin in cultured murine colon adenocarcinoma 26 (C-26) cells or C-26 cell-implanted mice. CONCLUSION: These results suggest that exenatide may be useful for treating peripheral neuropathy induced by oxaliplatin in colorectal cancer patients with type 2 diabetes. Public Library of Science 2015-11-04 /pmc/articles/PMC4633148/ /pubmed/26536615 http://dx.doi.org/10.1371/journal.pone.0141921 Text en © 2015 Fujita 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
Fujita, Shunsuke
Ushio, Soichiro
Ozawa, Nana
Masuguchi, Ken
Kawashiri, Takehiro
Oishi, Ryozo
Egashira, Nobuaki
Exenatide Facilitates Recovery from Oxaliplatin-Induced Peripheral Neuropathy in Rats
title Exenatide Facilitates Recovery from Oxaliplatin-Induced Peripheral Neuropathy in Rats
title_full Exenatide Facilitates Recovery from Oxaliplatin-Induced Peripheral Neuropathy in Rats
title_fullStr Exenatide Facilitates Recovery from Oxaliplatin-Induced Peripheral Neuropathy in Rats
title_full_unstemmed Exenatide Facilitates Recovery from Oxaliplatin-Induced Peripheral Neuropathy in Rats
title_short Exenatide Facilitates Recovery from Oxaliplatin-Induced Peripheral Neuropathy in Rats
title_sort exenatide facilitates recovery from oxaliplatin-induced peripheral neuropathy in rats
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4633148/
https://www.ncbi.nlm.nih.gov/pubmed/26536615
http://dx.doi.org/10.1371/journal.pone.0141921
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