Evidence map›Paper›PMID 31767624›Full record

ArticleJournal of the American Society of Nephrology : JASN2020

Drugs Repurposed as Antiferroptosis Agents Suppress Organ Damage, Including AKI, by Functioning as Lipid Peroxyl Radical Scavengers.

Eikan Mishima, Emiko Sato, Junya Ito, Ken-Ichi Yamada, Chitose Suzuki, Yoshitsugu Oikawa, Tetsuro Matsuhashi, Koichi Kikuchi, Takafumi Toyohara, Takehiro Suzuki and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of the American Society of Nephrology : JASN, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
101citing papers in PubMed, 2 pooled it
9.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

101 citing papers in PubMed, 2 syntheses or guidelines pooled it, 176 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Ferroptosis as a target mechanism in heart and kidney disease.The Journal of clinical investigation · 2026
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  19. Journal of clinical biochemistry and nutrition · 2025
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41 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 2 countries.

Eikan MishimaDivisions of Nephrology, Endocrinology, and Vascular Medicine and eikan@med.tohoku.ac.jp.ORCID 0000-0002-3706-2745
Emiko SatoDivisions of Nephrology, Endocrinology, and Vascular Medicine and.
Junya ItoFood and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
Ken-Ichi YamadaPhysical Chemistry for Life Science Laboratory, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Chitose SuzukiDivisions of Nephrology, Endocrinology, and Vascular Medicine and.
Yoshitsugu OikawaPediatrics, and.
Tetsuro MatsuhashiPediatrics, and.
Koichi KikuchiDivisions of Nephrology, Endocrinology, and Vascular Medicine and.
Takafumi ToyoharaDivisions of Nephrology, Endocrinology, and Vascular Medicine and.
Takehiro SuzukiDivisions of Nephrology, Endocrinology, and Vascular Medicine and.
Sadayoshi ItoDivisions of Nephrology, Endocrinology, and Vascular Medicine and.
Kiyotaka NakagawaFood and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
Takaaki AbeDivisions of Nephrology, Endocrinology, and Vascular Medicine and.ORCID 0000-0003-3170-4660
Center for Vascular Biology Research · USTohoku University · JPPediatrics and Genetics · USKyushu University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundFerroptosis, nonapoptotic cell death mediated by free radical reactions and driven by the oxidative degradation of lipids, is a therapeutic target because of its role in organ damage, including AKI. Ferroptosis-causing radicals that are targeted by ferroptosis suppressors have not been unequivocally identified. Because certain cytochrome P450 substrate drugs can prevent lipid peroxidation

methodsUsing a cell-based assay, we screened cytochrome P450 substrate compounds to identify drugs with antiferroptotic activity and investigated the underlying mechanism. To evaluate radical-scavenging activity, we used electron paramagnetic resonance-spin trapping methods and a fluorescence probe for lipid radicals, NBD-Pen, that we had developed. We then assessed the therapeutic potency of these drugs in mouse models of cisplatin-induced AKI and LPS/galactosamine-induced liver injury.

resultsWe identified various US Food and Drug Administration-approved drugs and hormones that have antiferroptotic properties, including rifampicin, promethazine, omeprazole, indole-3-carbinol, carvedilol, propranolol, estradiol, and thyroid hormones. The antiferroptotic drug effects were closely associated with the scavenging of lipid peroxyl radicals but not significantly related to interactions with other radicals. The elevated lipid peroxyl radical levels were associated with ferroptosis onset, and known ferroptosis suppressors, such as ferrostatin-1, also functioned as lipid peroxyl radical scavengers. The drugs exerted antiferroptotic activities in various cell types, including tubules, podocytes, and renal fibroblasts. Moreover, in mice, the drugs ameliorated AKI and liver injury, with suppression of tissue lipid peroxidation and decreased cell death.

conclusionsAlthough elevated lipid peroxyl radical levels can trigger ferroptosis onset, some drugs that scavenge lipid peroxyl radicals can help control ferroptosis-related disorders, including AKI.

Indexed as

Drug RepositioningAcute Kidney InjuryAnimalsCells, CulturedFerroptosisFree Radical ScavengersHumansLipid PeroxidationMaleMiceMice, Inbred C57BLRatsFree Radical Scavengersacute kidney injuryFerroptosislipid peroxidationPromethazineRegulated cell deathRifampicin

Identifiers

PMID31767624
PMCPMC7003311
OpenAlexW2990632313

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.