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ID 118743
Title Alternative
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
Author
Yoshioka, Toshihiko Tokushima University
Kanda, Masaya Tokushima University
Itobayashi, Sayuri Tokushima University
Sugimoto, Yugo Tokushima University
Miyata, Koji Tokushima University
Sakurada, Takumi Tokushima University
Keywords
cisplatin
adverse drug reaction
renal injury
valproic acid
proximal tubule cell
Content Type
Thesis or Dissertation
Description
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.
Journal Title
Clinical and Translational Science
ISSN
17528062
NCID
AA12625737
Publisher
Wiley|American Society for Clinical Pharmacology and Therapeutics
Volume
16
Issue
11
Start Page
2369
End Page
2381
Published Date
2023-09-12
Remark
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。
Rights
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.
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3762号
Diploma Number
甲医第1587号
Granted Date
2023-10-26
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
University Hospital
Medical Sciences