ID | 116131 |
Title Alternative | Role of ferroptosis in cisplatin-induced nephrotoxicity
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Author |
Ikeda, Yasumasa
Tokushima University
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Hamano, Hirofumi
Tokushima University
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Horinouchi, Yuya
Tokushima University
Hirayama, Tasuku
Gifu Pharmaceutical University
Nagasawa, Hideko
Gifu Pharmaceutical University
Tamaki, Toshiaki
Tokushima University|Anan-Medical Center
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Keywords | Cisplatin
Nephrotoxicity
Ferroptosis
Ferrous iron
Lipid peroxidation
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Content Type |
Journal Article
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Description | 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. |
Journal Title |
Journal of Trace Elements in Medicine and Biology
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ISSN | 0946672X
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NCID | AA12084444
AA11067337
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Publisher | Elsevier
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Volume | 67
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Start Page | 126798
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Published Date | 2021-05-28
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Rights | © 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/
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DOI (Published Version) | |
URL ( Publisher's Version ) | |
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language |
eng
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TextVersion |
Author
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departments |
Medical Sciences
Pharmaceutical Sciences
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