Dimethyl Fumarate Attenuates Oxaliplatin-Induced Peripheral Neuropathy without Affecting the Anti-tumor Activity of Oxaliplatin in Rodents
| Autor: | Nao Shigematsu, Daisuke Kobayashi, Takehiro Kawashiri, Anna Miyagi, Takao Shimazoe, Shiori Shimizu |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Dimethyl Fumarate medicine.medical_treatment Intraperitoneal injection Pharmaceutical Science Antineoplastic Agents Pharmacology medicine.disease_cause Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo Cell Line Tumor Neoplasms medicine Animals Mice Inbred BALB C Dimethyl fumarate business.industry Peripheral Nervous System Diseases General Medicine medicine.disease Sciatic Nerve digestive system diseases Tumor Burden Oxaliplatin stomatognathic diseases Neuroprotective Agents 030104 developmental biology Peripheral neuropathy Bone marrow suppression chemistry Hyperalgesia 030220 oncology & carcinogenesis medicine.symptom business Oxidative stress medicine.drug |
| Zdroj: | Biological and Pharmaceutical Bulletin. 42:638-644 |
| ISSN: | 1347-5215 0918-6158 |
| DOI: | 10.1248/bpb.b18-00855 |
| Popis: | Oxaliplatin has been used as a first choice for colorectal, gastric and pancreatic cancer, but it induces peripheral neuropathies. Dimethyl fumarate (DMF) is an oral drug for multiple sclerosis with neuroprotective effects on oxidative stress. Using both in vivo and in vitro models, we investigated the effects of DMF on oxaliplatin-induced peripheral neuropathy and other side effects, as well as on the anti-tumor activity of oxaliplatin. Repeated intraperitoneal injection of 4 mg/kg oxaliplatin (twice per week for 4 weeks) caused mechanical allodynia (as revealed by the von Frey tests), cold hyperalgesia (as revealed by the acetone tests), and axonal degeneration in the sciatic nerve of rats. Co-administration of oral DMF (200 mg/kg, five times per week for 4 weeks) relieved oxaliplatin-induced mechanical allodynia but not cold hyperalgesia, and ameliorated axonal degeneration. In addition, DMF did not exacerbate oxaliplatin-induced body weight loss or bone marrow suppression, such as reduction in red blood cells, white blood cells, neutrophils and lymphocytes. Furthermore, DMF did not inhibit the anti-tumor activity of oxaliplatin in any cultured cancer cell line (C26, mouse colon carcinoma; HCT116, human colon carcinoma; MKN45, human gastric adenocarcinoma; MIA PaCa-2, human pancreatic carcinoma) or C26-bearing mice. These results suggest that DMF prevents oxaliplatin-induced mechanical allodynia and axonal degeneration without affecting the anti-tumor activity of oxaliplatin. Therefore, DMF may be useful for managing oxaliplatin-induced chronic peripheral neuropathy. |
| Databáze: | OpenAIRE |
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