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ID 116131
タイトル別表記
Role of ferroptosis in cisplatin-induced nephrotoxicity
著者
堀ノ内, 裕也 Tokushima University
Hirayama, Tasuku Gifu Pharmaceutical University
永澤, 秀子 Gifu Pharmaceutical University
キーワード
Cisplatin
Nephrotoxicity
Ferroptosis
Ferrous iron
Lipid peroxidation
資料タイプ
学術雑誌論文
抄録
Background: Cisplatin is widely used as an antitumor drug for the treatment of solid tumors. However, its use has been limited owing to nephrotoxicity, a major side effect. The mechanism of cisplatin-induced nephrotoxicity (CIN) has long been investigated in order to develop preventive/therapeutic drugs. Ferroptosis is a newly identified form of non-apoptotic regulated cell death induced by iron-mediated lipid peroxidation and is involved in the pathophysiology of various diseases. In this study, we examined the role of ferroptosis in CIN.
Methods: We evaluated the role of ferroptosis in CIN by in vivo experiments in a mouse model.
Results: Cisplatin increased the protein expressions of transferrin receptor-1 and ferritin, and iron content in the kidney of mice. In addition, treatment with cisplatin augmented renal ferrous iron and hydroxyl radical levels with co-localization. Mice administered cisplatin demonstrated kidney injury, with renal dysfunction and increased inflammatory cytokine expression; these changes were ameliorated by Ferrostatin-1 (Fer-1), an inhibitor of ferroptosis. The expression of the ferroptosis markers, COX2 and 4-hydroxynonenal (4-HNE), increased with cisplatin administration, and decreased with the administration of Fer-1. By contrast, cisplatin-induced apoptosis and necroptosis were inhibited by treatment with Fer-1. Moreover, deferoxamine, an iron chelator, also inhibited CIN, with a decrease in the expression of COX-2 and 4-HNE.
Conclusion: Ferroptosis is involved in the pathogenesis of CIN and might be used as a new preventive target for CIN.
掲載誌名
Journal of Trace Elements in Medicine and Biology
ISSN
0946672X
cat書誌ID
AA12084444
AA11067337
出版者
Elsevier
67
開始ページ
126798
発行日
2021-05-28
備考
論文本文は2022-05-28以降公開予定
権利情報
© 2021. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
EDB ID
出版社版DOI
出版社版URL
言語
eng
著者版フラグ
その他
部局
医学系
薬学系