Ibudilast suppresses oxaliplatin-induced mechanical allodynia and neurodegeneration in rats

• Published in: Journal of pharmacological sciences 2021-09, Vol.147 (1), p.114-117
• Main Authors: Egashira, Nobuaki, Goto, Yu, Takahashi, Ryota, Iba, Hikari, Yamamoto, Shota, Watanabe, Takuya, Kubota, Kaori, Kawashiri, Takehiro, Taniguchi, Chise, Katsurabayashi, Shutaro, Iwasaki, Katsunori
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - pathology; Animals; Colonic Neoplasms - drug therapy; Colonic Neoplasms - pathology; Hyperalgesia - chemically induced; Hyperalgesia - pathology; Hyperalgesia - prevention & control; Ibudilast; Male; Mice; Oxaliplatin; Oxaliplatin - adverse effects; Oxaliplatin - therapeutic use; Peripheral Nervous System Diseases - chemically induced; Peripheral Nervous System Diseases - pathology; Peripheral Nervous System Diseases - prevention & control; Peripheral neuropathy; Phosphodiesterase Inhibitors - pharmacology; Phosphodiesterase Inhibitors - therapeutic use; Pyridines - pharmacology; Pyridines - therapeutic use; Rats; Rats, Sprague-Dawley; Tumor Cells, Cultured
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1016/j.jphs.2021.06.004

Oxaliplatin is a key drug used in the management of solid tumors, such as colorectal cancer; however, it causes peripheral neuropathy. In this study, we investigated the effect of ibudilast, a phosphodiesterase inhibitor, on oxaliplatin-induced mechanical allodynia and histological changes in rats. Ibudilast (7.5 mg/kg, i.p., 5 times per week) reduced mechanical allodynia and histological changes induced by oxaliplatin (4 mg/kg, i.p., twice a week). In contrast, ibudilast (0.01–10 μM) had no effect on oxaliplatin-induced tumor cytotoxicity in murine colon adenocarcinoma 26 cells. These findings suggest that ibudilast could be useful for preventing oxaliplatin-induced peripheral neuropathy in clinical settings.