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Exenatide Facilitates Recovery from Oxaliplatin-Induced Peripheral Neuropathy in Rats.

AbstractBACKGROUND:
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.
AuthorsShunsuke Fujita, Soichiro Ushio, Nana Ozawa, Ken Masuguchi, Takehiro Kawashiri, Ryozo Oishi, Nobuaki Egashira
JournalPloS one (PLoS One) Vol. 10 Issue 11 Pg. e0141921 ( 2015) ISSN: 1932-6203 [Electronic] United States
PMID26536615 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Hypoglycemic Agents
  • Organoplatinum Compounds
  • Peptides
  • Venoms
  • Oxaliplatin
  • Exenatide
Topics
  • Adenocarcinoma (drug therapy, pathology)
  • Animals
  • Antineoplastic Agents (toxicity)
  • Cell Survival (drug effects)
  • Colonic Neoplasms (drug therapy, pathology)
  • Exenatide
  • Hyperalgesia (chemically induced, drug therapy, pathology)
  • Hypoglycemic Agents (pharmacology)
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neurites (drug effects)
  • Organoplatinum Compounds (toxicity)
  • Oxaliplatin
  • PC12 Cells
  • Peptides (pharmacology)
  • Peripheral Nervous System Diseases (chemically induced, drug therapy, pathology)
  • Rats
  • Rats, Sprague-Dawley
  • Sciatic Nerve (cytology, drug effects)
  • Venoms (pharmacology)

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