ID | 118743 |
タイトル別表記 | バルプロ酸投与は近位尿細管障害を抑制することによりシスプラチン誘発腎障害を抑制する
VALPROIC ACID PROTECTS KIDNEYS FROM CISPLATIN
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著者 |
吉岡, 俊彦
徳島大学大学院医学研究科(医学専攻)
Kanda, Masaya
Tokushima University
Itobayashi, Sayuri
Tokushima University
Sugimoto, Yugo
Tokushima University
Miyata, Koji
Tokushima University
Sakurada, Takumi
Tokushima University
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キーワード | cisplatin
adverse drug reaction
renal injury
valproic acid
proximal tubule cell
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資料タイプ |
学位論文
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抄録 | Cisplatin treatment is effective against several types of carcinomas. However, it frequently leads to kidney injury, which warrants effective prevention methods. Sodium valproic acid is a prophylactic drug candidate with a high potential for clinical application against cisplatin-induced kidney injury. Therefore, in this study, we aimed to elucidate the mechanism underlying the prophylactic effect of valproic acid on cisplatin-induced kidney injury in a mouse model and HK2 and PODO cells with cisplatin-induced toxicity. In the mouse model of cisplatin-induced kidney injury, various renal function parameters and tubular damage scores were worsened by cisplatin, but they were significantly improved upon combination with valproic acid. No difference was observed in cisplatin accumulation between the cisplatin-treated and valproic acid-treated groups in whole blood and the kidneys. The mRNA expression levels of proximal tubular damage markers, apoptosis markers, and inflammatory cytokines significantly increased in the cisplatin group 72 h after cisplatin administration but significantly decreased upon combination with valproic acid. In HK2 cells, a human proximal tubular cell line, the cisplatin-induced decrease in cell viability was significantly suppressed by co-treatment with valproic acid. Valproic acid may inhibit cisplatin-induced kidney injury by suppressing apoptosis, inflammatory responses, and glomerular damage throughout the kidneys by suppressing proximal tubular cell damage. However, prospective controlled trials need to evaluate these findings before their practical application.
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掲載誌名 |
Clinical and Translational Science
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ISSN | 17528062
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cat書誌ID | AA12625737
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出版者 | Wiley|American Society for Clinical Pharmacology and Therapeutics
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巻 | 16
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号 | 11
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開始ページ | 2369
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終了ページ | 2381
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発行日 | 2023-09-12
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備考 | 内容要旨・審査要旨・論文本文の公開
本論文は,著者Toshihiko Yoshiokaの学位論文として提出され,学位審査・授与の対象となっている。 |
権利情報 | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
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EDB ID | |
出版社版DOI | |
出版社版URL | |
フルテキストファイル | |
言語 |
eng
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著者版フラグ |
博士論文全文を含む
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文科省報告番号 | 甲第3762号
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学位記番号 | 甲医第1587号
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学位授与年月日 | 2023-10-26
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学位名 |
博士(医学)
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学位授与機関 |
徳島大学
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部局 |
病院
医学系
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