Evidence map›Paper›PMID 41298719›Full record

ArticleScientific reports2025

Elucidation of puberulic acid-induced nephrotoxicity using stem cell-based kidney organoids.

Hiroyuki Nakanoh, Kenji Tsuji, Naruhiko Uchida, Kazuhiko Fukushima, Soichiro Haraguchi, Shinji Kitamura, Jun Wada

Abstract read
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
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

7 authors.

Hiroyuki NakanohDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Kenji TsujiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama, Japan. ktsuji@s.okayama-u.ac.jp.
Naruhiko UchidaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Kazuhiko FukushimaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Soichiro HaraguchiDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Shinji KitamuraDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama, Japan. sikitamura@hotmail.com.
Jun WadaDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Funding

Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science (JSPS) 24K11411
6 · The paper itself

Abstract

Recent cases of acute kidney injury (AKI) in Japan have been linked to Beni-koji CholesteHelp supplements, with puberulic acid identified as a potential nephrotoxic contaminant. To address the need for a reliable in vitro nephrotoxicity testing platform, we developed a screening model using kidney organoids derived from adult rat kidney stem (KS) cells. The organoids were exposed to known nephrotoxicants, including cisplatin and gentamicin, to validate the system. Puberulic acid toxicity was evaluated in both KS cell-derived organoids and wild-type mice. The organoids recapitulated tubular injury induced by known nephrotoxins and showed significant Kim-1 mRNA upregulation. Puberulic acid-treated organoids and mice exhibited morphological features of acute tubular necrosis (ATN), mitochondrial damage, and reduced cytochrome c oxidase subunit IV (COX-IV) expression. Markers of oxidative stress and apoptosis, such as 8-hydroxy-2'-deoxyguanosine (8-OHdG) and cleaved caspase-3, were also elevated. These findings suggest that puberulic acid induces mitochondrial dysfunction and oxidative stress, leading to tubular cell death. Puberulic acid-induced nephrotoxicity was demonstrated using our kidney organoid model. KS cell-derived kidney organoids may provide a simple, reproducible, and rapid platform for nephrotoxicity assessment, which may complement conventional animal experiments.

Indexed as

Acute Kidney InjuryKidneyOrganoidsStem CellsAnimalsApoptosisHepatitis A Virus Cellular Receptor 1MaleMiceMitochondriaOxidative StressRatsHepatitis A Virus Cellular Receptor 1Kidney organoidKidney stem cellMitochondrial dysfunctionNephrotoxicityPuberulic acid

Identifiers

PMID41298719
PMCPMC12658070

What Socratic holds

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LicenceCC BY
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Registered trials

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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 Socratic graph.