論文 - 詳細
| RRC ID | 52471 |
|---|---|
| 著者 | Ishii N, Tsubouchi H, Miura A, Yanagi S, Ueno H, Shiomi K, Nakazato M. |
| タイトル | Ghrelin alleviates paclitaxel-induced peripheral neuropathy by reducing oxidative stress and enhancing mitochondrial anti-oxidant functions in mice. |
| ジャーナル | Eur J Pharmacol |
| Abstract |
Paclitaxel is an effective chemotherapeutic agent, but has some treatment-limiting adverse effects that markedly decrease patients' quality of life. Peripheral neuropathy is one of these, and no treatment for it has been established yet. Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, is secreted from the stomach and has widespread effects on multiple systems. We investigated the pharmacological potential of ghrelin in preventing paclitaxel-induced peripheral neuropathy using wild-type mice, ghrelin-null mice, and growth hormone secretagogue receptor-null mice. In wild-type mice, ghrelin administration alleviated mechanical and thermal hypersensitivity, and partially prevented neuronal loss of small unmyelinated intraepidermal nerve fibers but not large myelinated nerve fibers. Moreover, ghrelin administration decreased plasma oxidative and nitrosative stress and increased the expression of uncoupling protein 2 (UCP2) and superoxide dismutase 2 (SOD2) in the dorsal root ganglia, which are mitochondrial antioxidant proteins, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a regulator of mitochondrial number. Both ghrelin-null mice and growth hormone secretagogue receptor-null mice developed more severe nerve injuries than wild-type mice. Our results suggest that ghrelin administration exerts a protective effect against paclitaxel-induced neuropathy by reducing oxidative stress and enhancing mitochondrial anti-oxidant functions, and that endogenous ghrelin has a neuroprotective effect that is mediated by ghrelin/growth hormone secretagogue receptor signaling. Ghrelin could be a promising therapeutic agent for the management of this intractable disease. |
| 巻・号 | 819 |
| ページ | 35-42 |
| 公開日 | 2018-1-15 |
| DOI | 10.1016/j.ejphar.2017.11.024 |
| PII | S0014-2999(17)30757-4 |
| PMID | 29154935 |
| MeSH | Animals Antioxidants / metabolism* Ganglia, Spinal / drug effects Ganglia, Spinal / metabolism Ganglia, Spinal / pathology Gene Expression Regulation / drug effects Ghrelin / pharmacology* Ghrelin / therapeutic use Male Mice Mice, Inbred C57BL Mitochondria / drug effects* Mitochondria / metabolism* Mitochondrial Proteins / metabolism Neuroprotective Agents / pharmacology Neuroprotective Agents / therapeutic use Oxidative Stress / drug effects* PC12 Cells Paclitaxel / adverse effects* Peripheral Nerves / drug effects Peripheral Nervous System Diseases / chemically induced Peripheral Nervous System Diseases / drug therapy* Peripheral Nervous System Diseases / metabolism Peripheral Nervous System Diseases / pathology Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics RNA, Messenger / genetics RNA, Messenger / metabolism Rats Receptors, Ghrelin / metabolism Superoxide Dismutase / genetics Superoxide Dismutase / metabolism Uncoupling Protein 2 / genetics |
| IF | 3.263 |
| 引用数 | 14 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | PC-12(RCB0009) |