Evidence map›Paper›PMID 42573955›Full record

ArticleClinical and experimental nephrology2026

5-hydroxy-1-methylhydantoin (NZ-419), an endogenous antioxidant, attenuates mycotoxin-induced oxidative stress in human kidney proximal tubular epithelial cells.

Ebenezer Ofori-Attah, Mai Hashimoto, Mayu Oki, Hisao Kansui, Hitoshi Maeda, Shoko Okazaki, Keizo Takeshita, Daisuke Kadowaki

Abstract read
PubMed Publisher
In one paragraph

Article in Clinical and experimental nephrology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

8 authors.

Ebenezer Ofori-AttahGraduate School of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, 860-0082, Kumamoto, Japan.ORCID http://orcid.org/0000-0002-4371-3698
Mai HashimotoGraduate School of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, 860-0082, Kumamoto, Japan.
Mayu OkiGraduate School of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, 860-0082, Kumamoto, Japan.
Hisao KansuiGraduate School of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, 860-0082, Kumamoto, Japan.
Hitoshi MaedaLaboratory of Biopharmaceutics, Kyoto Pharmaceutical University, Kyoto, Japan.
Shoko OkazakiGraduate School of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, 860-0082, Kumamoto, Japan.
Keizo TakeshitaGraduate School of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, 860-0082, Kumamoto, Japan.
Daisuke KadowakiGraduate School of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, 860-0082, Kumamoto, Japan. d-kado@ph.sojo-u.ac.jp.ORCID http://orcid.org/0000-0001-5166-7145

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundExposure to foodborne mycotoxins such as ochratoxin A (OTA) and citrinin (CIT) causes severe oxidative stress-mediated nephropathy. This study investigated the protective potential of 5-hydroxy-1-methylhydantoin (NZ-419), an endogenous creatinine metabolite, against OTA- and CIT-induced toxicity in human proximal tubular epithelial (HK-2) cells.

methodsWe evaluated the radical-scavenging activity of NZ-419 using cell-free assays, including electron spin resonance. In HK-2 cells, its effects on mycotoxin-induced cytotoxicity, reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP), and related signaling pathways were assessed using biochemical assays, Western blotting, and qPCR. The effects of NZ-419 on hypoxia-reoxygenation-induced cellular stress were also examined.

resultsNZ-419 selectively scavenged hydroxyl radicals and peroxynitrite. In HK-2 cells, it significantly attenuated OTA-induced cytotoxicity. While not fully restoring viability in CIT-treated cells, it effectively mitigated oxidative stress induced by both mycotoxins. NZ-419 prevented MMP depolarization and upregulated Bcl-2, indicating anti-apoptotic potential. It suppressed ROS overproduction and NADPH oxidase 4 (NOX4) expression while activating the Keap1-Nrf2 pathway, upregulating antioxidant genes (SOD1, CAT, and GPx). Furthermore, NZ-419 reduced HIF-1α and CTGF expression under both mycotoxin-induced and hypoxia-reoxygenation conditions.

conclusionNZ-419 selectively scavenges toxic radicals and attenuates mycotoxin-induced oxidative stress and mitochondrial dysfunction in HK-2 cells. These findings provide mechanistic evidence for the protective effects of NZ-419 and support its potential as a renoprotective agent against oxidative stress-related kidney injury.

Indexed as

AntioxidantsCitrininEpithelial CellsHydantoinsKidney Tubules, ProximalOchratoxinsOxidative StressCell LineCell SurvivalHumansMembrane Potential, MitochondrialNADPH Oxidase 4NF-E2-Related Factor 2Reactive Oxygen SpeciesSignal TransductionAntioxidantsCitrininHydantoinsNADPH Oxidase 4NFE2L2 protein, humanNF-E2-Related Factor 2ochratoxin AOchratoxinsReactive Oxygen Species5-hydroxy-1-methylhydantoin (NZ-419)AntioxidantCitrininKidney diseaseOchratoxin AOxidative Stress

Identifiers

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.