Improvement of peripheral vascular impairment by a phosphodiesterase type 5 inhibitor tadalafil prevents oxaliplatin-induced peripheral neuropathy in mice
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- Ogihara, Takashi
- Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital
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- Nakagawa, Takayuki
- Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital
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- Hayashi, Maho
- Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital
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- Koyanagi, Madoka
- Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital
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- Yonezawa, Atsushi
- Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital・Graduate School of Pharmaceutical Sciences, Kyoto University
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- Omura, Tomohiro
- Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital
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- Nakagawa, Shunsaku
- Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital
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- Kitada, Noriaki
- Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital
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- Imai, Satoshi
- Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital
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- Matsubara, Kazuo
- Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital
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Abstract
Oxaliplatin, a platinum-based chemotherapeutic drug, frequently induces peripheral neuropathy. Accumulating evidences suggest a possible relationship between peripheral vascular impairment and peripheral neuropathy. In this study, we investigated the effects of vasodilators on cumulative peripheral neuropathy induced by repeated injections of oxaliplatin (10 mg/kg) once a week for 8 weeks in mice. Single injections of vasodilators, including a phosphodiesterase type 5 inhibitor tadalafil acutely alleviated oxaliplatin-induced cold hypersensitivity, while tadalafil had no effect on the mechanical hypersensitivity. By contrast, long-term administration of tadalafil (0.1% in chow diets) during the oxaliplatin injection period reduced the oxaliplatin-induced decreases in skin temperature and blood flow without affecting platinum concentrations in blood, sciatic nerves, and dorsal root ganglion. The long-term administration significantly suppressed cold, mechanical, and electrical current hypersensitivities as well as thermal hypoesthesia. Furthermore, it prevented the decreases in sensory nerve conductance velocity and the number of endoneurial microvessels, and axon degeneration in the sciatic nerves. In vitro studies confirmed that tadalafil does not interfere with the cytotoxicity of oxaliplatin against human cancer cell lines. Altogether, these results suggest that improvement of peripheral vascular impairment by tadalafil could alleviate and prevent oxaliplatin-induced peripheral neuropathy.
Journal
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- Journal of Pharmacological Sciences
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Journal of Pharmacological Sciences 141 (4), 131-138, 2019-12
Japanese Pharmacological Society
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Details 詳細情報について
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- CRID
- 1050566774746910080
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- NII Article ID
- 120006844940
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- ISSN
- 13478613
- 13478648
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- HANDLE
- 2433/250979
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- Text Lang
- en
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- Article Type
- journal article
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- Data Source
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- IRDB
- Crossref
- CiNii Articles
- KAKEN