number of access : ?
number of downloads : ?
ID 115399
Title Alternative
Efficacy of diphenhydramine as a preventive medicine against cisplatin-induced nephrotoxicity
Diphenhydramine against cisplatin nephrotoxicity
Author
Kishi, Seiji Tokushima University|Kawasaki Medical School KAKEN Search Researchers
Chuma, Masayuki Tokushima University
Niimura, Takahiro Tokushima University
Imanishi, Masaki Tokushima University
Horinouchi, Yuya Tokushima University
Keywords
cisplatin
nephrotoxicity
diphenhydramine
Content Type
Journal Article
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.
Journal Title
Kidney International
ISSN
00852538
NCID
AA00710996
AA11629608
Publisher
Elsevier|International Society of Nephrology
Volume
99
Issue
4
Start Page
885
End Page
899
Published Date
2020-12-09
Remark
論文本文は2021-12-09以降公開予定
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/
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
language
eng
TextVersion
その他
departments
Medical Sciences
University Hospital
Pharmaceutical Sciences