title: Exenatide Facilitates Recovery from Oxaliplatin-Induced Peripheral Neuropathy in Rats.
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 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.
  
  
  CONCLUSIONS
  These results suggest that exenatide may be useful for treating peripheral neuropathy induced by oxaliplatin in colorectal cancer patients with type 2 diabetes.
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Fujita
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Ushio
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Nana
authors.initials: N
authors.lastname: Ozawa
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Masuguchi
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Kawashiri
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Ryozo
authors.initials: R
authors.lastname: Oishi
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Egashira
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077270:Exenatide; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016501:Neurites / Q000187:drug effects; D009944:Organoplatinum Compounds / Q000633:toxicity*; D000077150:Oxaliplatin; D016716:PC12 Cells; D010455:Peptides / Q000494:pharmacology*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000166:cytology / Q000187:drug effects; D014688:Venoms / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D007004:Hypoglycemic Agents; D009944:Organoplatinum Compounds; D010455:Peptides; D014688:Venoms; D000077150:Oxaliplatin; D000077270:Exenatide