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ID 115399
タイトル別表記
Efficacy of diphenhydramine as a preventive medicine against cisplatin-induced nephrotoxicity
Diphenhydramine against cisplatin nephrotoxicity
著者
岸, 誠司 Tokushima University|Kawasaki Medical School KAKEN研究者をさがす
中馬, 真幸 Tokushima University
Niimura, Takahiro Tokushima University
武智, 研志 Tokushima University
今西, 正樹 Tokushima University
堀ノ内, 裕也 Tokushima University
キーワード
cisplatin
nephrotoxicity
diphenhydramine
資料タイプ
学術雑誌論文
抄録
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.
掲載誌名
Kidney International
ISSN
00852538
cat書誌ID
AA00710996
AA11629608
出版者
Elsevier|International Society of Nephrology
99
4
開始ページ
885
終了ページ
899
発行日
2020-12-09
備考
論文本文は2021-12-09以降公開予定
権利情報
© 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
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
病院
薬学系