Exenatide facilitates recovery from oxaliplatin-induced peripheral neuropathy in rats

Shunsuke Fujita, Soichiro Ushio, Nana Ozawa, Ken Masuguchi, takehiro kawashiri, Ryozo Oishi, Nobuaki Egashira

Research output: Contribution to journalArticle

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Abstract

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 oxaliplatininduced 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.

Original languageEnglish
Article number141921
JournalPloS one
Volume10
Issue number11
DOIs
Publication statusPublished - Nov 4 2015

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oxaliplatin
peripheral nervous system diseases
Peripheral Nervous System Diseases
Rats
Recovery
rats
neurites
Hyperalgesia
cells
colorectal neoplasms
noninsulin-dependent diabetes mellitus
agonists
Pheochromocytoma
Medical problems
secretin
glucagon-like peptide 1
toluidine blue
neuroprotective effect
peripheral nervous system
Type 2 Diabetes Mellitus

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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Exenatide facilitates recovery from oxaliplatin-induced peripheral neuropathy in rats. / Fujita, Shunsuke; Ushio, Soichiro; Ozawa, Nana; Masuguchi, Ken; kawashiri, takehiro; Oishi, Ryozo; Egashira, Nobuaki.

In: PloS one, Vol. 10, No. 11, 141921, 04.11.2015.

Research output: Contribution to journalArticle

Fujita, Shunsuke ; Ushio, Soichiro ; Ozawa, Nana ; Masuguchi, Ken ; kawashiri, takehiro ; Oishi, Ryozo ; Egashira, Nobuaki. / Exenatide facilitates recovery from oxaliplatin-induced peripheral neuropathy in rats. In: PloS one. 2015 ; Vol. 10, No. 11.
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