論文 - 詳細
| RRC ID | 68070 |
|---|---|
| 著者 | Fujita S, Ushio S, Ozawa N, Masuguchi K, Kawashiri T, Oishi R, Egashira N. |
| タイトル | Exenatide Facilitates Recovery from Oxaliplatin-Induced Peripheral Neuropathy in Rats. |
| ジャーナル | PLoS One |
| 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. CONCLUSION:These results suggest that exenatide may be useful for treating peripheral neuropathy induced by oxaliplatin in colorectal cancer patients with type 2 diabetes. |
| 巻・号 | 10(11) |
| ページ | e0141921 |
| 公開日 | 2015-1-1 |
| DOI | 10.1371/journal.pone.0141921 |
| PII | PONE-D-15-30370 |
| PMID | 26536615 |
| PMC | PMC4633148 |
| MeSH | Adenocarcinoma / drug therapy* Adenocarcinoma / pathology Animals Antineoplastic Agents / toxicity Cell Survival / drug effects* Colonic Neoplasms / drug therapy* Colonic Neoplasms / pathology Exenatide Hyperalgesia / chemically induced Hyperalgesia / drug therapy* Hyperalgesia / 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 Peripheral Nervous System Diseases / drug therapy* Peripheral Nervous System Diseases / pathology Rats Rats, Sprague-Dawley Sciatic Nerve / cytology Sciatic Nerve / drug effects Venoms / pharmacology* |
| IF | 2.74 |
| リソース情報 | |
| ヒト・動物細胞 | PC-12(RCB0009) Colon-26(RCB2657) |