ID | 115399 |
Title Alternative | Efficacy of diphenhydramine as a preventive medicine against cisplatin-induced nephrotoxicity
Diphenhydramine against cisplatin nephrotoxicity
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Author |
Hamano, Hirofumi
Tokushima University
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Ikeda, Yasumasa
Tokushima University
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Goda, Mitsuhiro
Tokushima University
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Fukushima, Keijo
Tokushima University
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Chuma, Masayuki
Tokushima University
Niimura, Takahiro
Tokushima University
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Takechi, Kenshi
Tokushima University
Horinouchi, Yuya
Tokushima University
Izawa-Ishizawa, Yuki
Tokushima University
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Ishizawa, Keisuke
Tokushima University
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Tamaki, Toshiaki
Tokushima University|Anan-Medical Center
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Keywords | cisplatin
nephrotoxicity
diphenhydramine
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Content Type |
Journal Article
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Description | Cisplatin is widely used as an anti-tumor drug for the treatment of solid tumors. Unfortunately, it causes nephrotoxicity as a critical side effect, limiting its use, given that no preventive drug against cisplatin-induced nephrotoxicity is currently available. This study identified that a previously developed drug, diphenhydramine, may provide a novel treatment for cisplatin-induced nephrotoxicity based on the results of the analysis of medical big data. We evaluated the actual efficacy of diphenhydramine via in vitro and in vivo experiments in a mouse model. Diphenhydramine inhibited cisplatin-induced cell death in renal proximal tubular cells. Mice administered cisplatin developed kidney injury with renal dysfunction (plasma creatinine: 0.43 ± 0.04 mg/dl vs 0.15 ± 0.01 mg/dl, p<0.01) and showed augmented oxidative stress, increased apoptosis, elevated inflammatory cytokines, and mitogen-activated protein kinases activation; however, most of these symptoms were suppressed by treatment with diphenhydramine. Further, the renal concentration of cisplatin was attenuated in diphenhydramine-treated mice (platinum content: 70.0 ± 3.3 µg/g dry kidney weight vs 53.4 ± 3.6 µg/g dry kidney weight, p<0.05). Importantly, diphenhydramine did not influence or interfere with the anti-tumor effect of cisplatin in any of the in vitro or in vivo experiments. Moreover, a retrospective clinical study of 1467 cancer patients treated with cisplatin showed that patients who had used diphenhydramine exhibited less acute kidney injury than patients who had not used diphenhydramine (6.1 % vs 22.4 %, p<0.05). Thus, diphenhydramine demonstrated efficacy as a novel preventive medicine against cisplatin-induced nephrotoxicity.
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Journal Title |
Kidney International
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ISSN | 00852538
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NCID | AA00710996
AA11629608
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Publisher | Elsevier|International Society of Nephrology
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Volume | 99
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Issue | 4
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Start Page | 885
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End Page | 899
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Published Date | 2020-12-09
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Rights | © 2020. 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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EDB ID | |
DOI (Published Version) | |
URL ( Publisher's Version ) | |
FullText File | |
language |
eng
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TextVersion |
Author
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departments |
Medical Sciences
University Hospital
Pharmaceutical Sciences
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