Cargando…
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...
Autores principales: | , , , , , , |
---|---|
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 |
_version_ | 1782399159647600640 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4633148 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT fujitashunsuke exenatidefacilitatesrecoveryfromoxaliplatininducedperipheralneuropathyinrats AT ushiosoichiro exenatidefacilitatesrecoveryfromoxaliplatininducedperipheralneuropathyinrats AT ozawanana exenatidefacilitatesrecoveryfromoxaliplatininducedperipheralneuropathyinrats AT masuguchiken exenatidefacilitatesrecoveryfromoxaliplatininducedperipheralneuropathyinrats AT kawashiritakehiro exenatidefacilitatesrecoveryfromoxaliplatininducedperipheralneuropathyinrats AT oishiryozo exenatidefacilitatesrecoveryfromoxaliplatininducedperipheralneuropathyinrats AT egashiranobuaki exenatidefacilitatesrecoveryfromoxaliplatininducedperipheralneuropathyinrats |