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Ghrelin alleviates paclitaxel-induced peripheral neuropathy by reducing oxidative stress and enhancing mitochondrial anti-oxidant functions in mice
http://hdl.handle.net/10458/6668
http://hdl.handle.net/10458/6668e266b21c-c1ef-4b4e-bd24-95e1d44b5578
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youshi.pdf (2.2 MB)
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shinsakekka.pdf (613.4 kB)
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honbun.pdf (1.7 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2020-06-21 | |||||
| タイトル | ||||||
| タイトル | Ghrelin alleviates paclitaxel-induced peripheral neuropathy by reducing oxidative stress and enhancing mitochondrial anti-oxidant functions in mice | |||||
| タイトル | ||||||
| タイトル | グレリンは酸化ストレスを減少させミトコンドリアの抗酸化能を増強させることでマウスのパクリタキセノレ誘導性末梢神経障害を緩和させる | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Ghrelin, Growth hormone secretagogue receptor, Paclitaxel, Chemotherapy-induced peripheral neuropathy, Peripheral neuropathic pain, PC12 | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||
| 資源タイプ | doctoral thesis | |||||
| アクセス権 | ||||||
| アクセス権 | open access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
| 著者 |
石井, 信之
× 石井, 信之× Ishii, Nobuyuki |
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| 公開者 | ||||||
| 出版者 | Elsevier | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | 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. | |||||
| 内容記述 | ||||||
| 以下に掲載: European Journal of Pharmacology .2018,Volume 819.pages 35-42 | ||||||
| 学位名 | ||||||
| 学位名 | 博士(医学) | |||||
| 学位授与機関 | ||||||
| 学位授与機関識別子Scheme | kakenhi | |||||
| 学位授与機関識別子 | 17601 | |||||
| 学位授与機関名 | 宮崎大学 | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2019-03-22 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 甲第86号 | |||||
| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
