直近一年間の累計
アクセス数 : ?
ダウンロード数 : ?
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
武智, 研志 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
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
フルテキストファイル
言語
eng
著者版フラグ
著者版
部局
医学系
病院
薬学系