Valproic acid treatment attenuates cisplatin-induced kidney injury by suppressing proximal tubular cell damage

• Material Type: 博士論文
• Title: Valproic acid treatment attenuates cisplatin-induced kidney injury by suppressing proximal tubular cell damage
• Author/Editor: Yoshioka, Toshihiko; Goda, Mitsuhiro; Kanda, Masaya; Itobayashi, Sayuri; Sugimoto, Yugo; Izawa-Ishizawa, Yuki; Yagi, Kenta; Aizawa, Fuka; Miyata, Koji; Niimura, Takahiro; Hamano, Hirofumi; Sakurada, Takumi; Zamami, Yoshito; Ishizawa, Keisuke
• Author Heading: Yoshioka, Toshihiko; Goda, Mitsuhiro; Kanda, Masaya; Itobayashi, Sayuri; Sugimoto, Yugo; Izawa-Ishizawa, Yuki; Yagi, Kenta; Aizawa, Fuka; Miyata, Koji; Niimura, Takahiro; Hamano, Hirofumi; Sakurada, Takumi; Zamami, Yoshito; Ishizawa, Keisuke
• Publication, Distribution, etc.: Wiley|American Society for Clinical Pharmacology and Therapeutics
• Publication Date: 2023-09-12
• Publication Date (W3CDTF): 2023-09-12
• Alternative Title: 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
• Periodical title: Clinical and Translational Science
• No. or year of volume/issue: 16 11
• Volume: 16
• Issue: 11
• Pages: 2369-2381
• ISSN (Periodical Title): ISSN : 1752-8062
• Degree grantor/type: 徳島大学
• Date Granted: 2023-10-26
• Dissertation Number: 甲第3762号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: cisplatin; adverse drug reaction; renal injury; valproic acid; proximal tubule cell
• Target Audience: 一般
• Note (General): 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.
• Access Restrictions: インターネット公開
• Rights (production): 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.
• Related Material (DOI): 10.1111/cts.13638
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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http://repo.lib.tokushima-u.ac.jp/files/public/11/118743/2023111609594789614/k3762_abstract.pdf fulltext

http://repo.lib.tokushima-u.ac.jp/files/public/11/118743/20231116095947190157/k3762_review.pdf fulltext

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