RRC ID 77037
Author Shigematsu N, Kawashiri T, Kobayashi D, Shimizu S, Mine K, Hiromoto S, Uchida M, Egashira N, Shimazoe T.
Title Neuroprotective effect of alogliptin on oxaliplatin-induced peripheral neuropathy in vivo and in vitro.
Journal Sci Rep
Abstract 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.
Volume 10(1)
Pages 6734
Published 2020-4-21
DOI 10.1038/s41598-020-62738-w
PII 10.1038/s41598-020-62738-w
PMID 32317735
PMC PMC7174301
MeSH Allografts Animals Antineoplastic Agents / adverse effects* Axons / drug effects Axons / pathology Cell Differentiation / drug effects Cell Line, Tumor Cisplatin / adverse effects* Colonic Neoplasms / drug therapy Colonic Neoplasms / pathology Dose-Response Relationship, Drug HCT116 Cells Humans Hyperalgesia / chemically induced Hyperalgesia / physiopathology Hyperalgesia / prevention & control* Male Mice Mice, Inbred BALB C Neurites / drug effects Neurites / pathology Neuroprotective Agents / pharmacology* Oxaliplatin / adverse effects* PC12 Cells Peripheral Nervous System Diseases / chemically induced Peripheral Nervous System Diseases / physiopathology Peripheral Nervous System Diseases / prevention & control* Piperidines / pharmacology* Rats Rats, Sprague-Dawley Sciatic Nerve / drug effects Sciatic Nerve / physiopathology Tumor Burden / drug effects Uracil / analogs & derivatives* Uracil / pharmacology
IF 3.998
Human and Animal Cells HCT116(RCB2979)