Neuroprotective effect of alogliptin on oxaliplatin-induced peripheral neuropathy in vivo and in vitro
Autor: | Keisuke Mine, Nobuaki Egashira, Takao Shimazoe, Takehiro Kawashiri, Mayako Uchida, Nao Shigematsu, Daisuke Kobayashi, Shiori Hiromoto, Shiori Shimizu |
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Rok vydání: | 2019 |
Předmět: |
Male
lcsh:Medicine Antineoplastic Agents Pharmacology Neuroprotection PC12 Cells Article Rats Sprague-Dawley Mice Piperidines In vivo Pancreatic cancer Cell Line Tumor medicine Neurites Animals Humans Chemotherapy Neurodegeneration lcsh:Science Uracil Dipeptidyl peptidase-4 Cisplatin Mice Inbred BALB C Multidisciplinary Dose-Response Relationship Drug business.industry lcsh:R Peripheral Nervous System Diseases Cell Differentiation medicine.disease Allografts HCT116 Cells Sciatic Nerve digestive system diseases Axons Oxaliplatin Rats Tumor Burden Peripheral neuropathy Neuroprotective Agents Hyperalgesia Colonic Neoplasms lcsh:Q business Alogliptin medicine.drug |
Zdroj: | Scientific Reports Scientific Reports, Vol 10, Iss 1, Pp 1-8 (2020) |
ISSN: | 2045-2322 |
Popis: | Oxaliplatin is a platinum-based antineoplastic drug commonly used for treating colorectal, gastric, and pancreatic cancer. However, it frequently causes peripheral neuropathy as dose-limiting toxicity and is lacking a strategy for prevention. Alogliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, is an oral antidiabetic drug. Previous studies have shown that DPP-4 inhibitors have pleiotropic effects, including neuroprotection. In this study, we investigated the effects of alogliptin on oxaliplatin-induced peripheral neuropathy using in vitro and in vivo models. In PC12 cells, alogliptin attenuated neurite disorders induced by oxaliplatin and cisplatin. The repeated injection of oxaliplatin caused mechanical allodynia and axonal degeneration of the sciatic nerve in rats. These neuropathies were ameliorated by co-administration of alogliptin. Moreover, alogliptin did not attenuate tumor cytotoxicity of oxaliplatin in the cultured colon, gastric, or pancreatic cancer cell lines and tumor-bearing mice. These findings suggest that alogliptin may be beneficial for preventing oxaliplatin-induced peripheral neuropathy. |
Databáze: | OpenAIRE |
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