論文

査読有り 国際誌
2021年4月

Diphenhydramine may be a preventive medicine against cisplatin-induced kidney toxicity.

Kidney international
  • Hirofumi Hamano
  • Yasumasa Ikeda
  • Mitsuhiro Goda
  • Keijo Fukushima
  • Seiji Kishi
  • Masayuki Chuma
  • Michiko Yamashita
  • Takahiro Niimura
  • Kenshi Takechi
  • Masaki Imanishi
  • Yoshito Zamami
  • Yuya Horinouchi
  • Yuki Izawa-Ishizawa
  • Licht Miyamoto
  • Keisuke Ishizawa
  • Hiromichi Fujino
  • Toshiaki Tamaki
  • Ken-Ichi Aihara
  • Koichiro Tsuchiya
  • 全て表示

99
4
開始ページ
885
終了ページ
899
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.kint.2020.10.041

Cisplatin is widely used as an anti-tumor drug for the treatment of solid tumors. Unfortunately, it causes kidney toxicity as a critical side effect, limiting its use, given that no preventive drug against cisplatin-induced kidney toxicity is currently available. Here, based on a repositioning analysis of the Food and Drug Administration Adverse Events Reporting System, we found that a previously developed drug, diphenhydramine, may provide a novel treatment for cisplatin-induced kidney toxicity. To confirm this, the actual efficacy of diphenhydramine was evaluated in in vitro and in vivo experiments. Diphenhydramine inhibited cisplatin-induced cell death in kidney proximal tubular cells. Mice administered cisplatin developed kidney injury with significant dysfunction (mean plasma creatinine: 0.43 vs 0.15 mg/dl) and showed augmented oxidative stress, increased apoptosis, elevated inflammatory cytokines, and MAPKs activation. However, most of these symptoms were suppressed by treatment with diphenhydramine. Furthermore, the concentration of cisplatin in the kidney was significantly attenuated in diphenhydramine-treated mice (mean platinum content: 70.0 vs 53.4 μg/g dry kidney weight). Importantly, diphenhydramine did not influence or interfere with the anti-tumor effect of cisplatin in any of the in vitro or in vivo experiments. In a selected cohort of 98 1:1 matched patients from a retrospective database of 1467 patients showed that patients with malignant cancer who had used diphenhydramine before cisplatin treatment exhibited significantly less acute kidney injury compared to ones who did not (6.1 % vs 22.4 %, respectively). Thus, diphenhydramine demonstrated efficacy as a novel preventive medicine against cisplatin-induced kidney toxicity.

リンク情報
DOI
https://doi.org/10.1016/j.kint.2020.10.041
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/33307103
URL
https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=372231
ID情報
  • DOI : 10.1016/j.kint.2020.10.041
  • ISSN : 0085-2538
  • PubMed ID : 33307103

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