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Diphenhydramine may be a preventive medicine against cisplatin-induced kidney toxicity.
- Source :
-
Kidney international [Kidney Int] 2021 Apr; Vol. 99 (4), pp. 885-899. Date of Electronic Publication: 2020 Dec 09. - Publication Year :
- 2021
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Abstract
- 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.<br /> (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Apoptosis
Cisplatin toxicity
Diphenhydramine metabolism
Diphenhydramine pharmacology
Diphenhydramine therapeutic use
Humans
Kidney metabolism
Mice
Oxidative Stress
Retrospective Studies
Acute Kidney Injury chemically induced
Acute Kidney Injury drug therapy
Acute Kidney Injury prevention & control
Antineoplastic Agents toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 1523-1755
- Volume :
- 99
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Kidney international
- Publication Type :
- Academic Journal
- Accession number :
- 33307103
- Full Text :
- https://doi.org/10.1016/j.kint.2020.10.041