{
  "abstract": "Background/Objectives Calcium oxalate (CaOx) crystals contribute to renal tubular injury in nephrolithiasis, but the relationship among NADPH oxidase (NOX), oxidative stress, ferroptosis-related injury, and PI3K/AKT signaling remains incompletely defined. We examined CaOx-induced injury in NRK-52E renal tubular epithelial cells and tested the effects of pharmacological NOX and PI3K inhibition on oxidative and ferroptosis-related readouts.Methods NRK-52E cells were exposed to CaOx (0–10 mM) and assessed by CCK-8, DCFH-DA flow cytometry, NOX activity assay, NADPH and Fe2+ assays, GSH and malondialdehyde (MDA) assays, quantitative real-time PCR (qRT-PCR), Western blotting, and transcriptome sequencing. Ferrostatin-1 (Fer-1, 2 μM), Erastin (10 μM), the NOX inhibitor GKT137831 (10 μM), and the PI3K inhibitor LY294002 (10 μM) were used as pharmacological probes.Results CaOx reduced cell viability and increased intracellular ROS in a concentration-dependent manner. At 1 mM, CaOx was associated with lower NADPH and GSH, higher Fe2+, MDA, and ROS, increased NOX activity and NOX4 mRNA and protein expression, reduced GPX4, and increased ACSL4. Fer-1 ameliorated, whereas Erastin aggravated, several ferroptosis-associated readouts. CaOx also increased the p-PI3K/PI3K and p-AKT/AKT ratios. GKT137831 and LY294002 each attenuated CaOx-associated oxidative stress and ferroptosis-related phenotypes in this cell model.Conclusions The findings support a contribution of NOX-associated oxidative stress and ferroptosis-related injury to CaOx-exposed NRK-52E cells. Pharmacological experiments indicate that NOX and PI3K/AKT signaling participate in this phenotype. These findings are limited to an in vitro cell model and require validation in animal and human-relevant systems.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Emergency, The Third People’s Hospital of Hefei, Hefei, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ming Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Ning Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhenyu Geng"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6eqhmrdaqnrfw.bib",
  "cited_by": 0,
  "doi": "10.1080/0886022x.2026.2750582",
  "fulltext_url": "https://www.tandfonline.com/doi/10.1080/0886022X.2026.2750582",
  "id": "6eqhmrdaqnrfw",
  "issns": [
    "1525-6049",
    "0886-022X"
  ],
  "landing_url": "https://doi.org/10.1080/0886022x.2026.2750582",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Nephrolithiasis and Urolithiasis"
    ],
    [
      "heading",
      "Research Article"
    ],
    [
      "lcc",
      "RC870-923"
    ],
    [
      "openalex",
      "2740|Kidney Stones and Urolithiasis Treatments"
    ]
  ],
  "openalex": "W7224819060",
  "pdf_url": null,
  "pmcid": "PMC13726258",
  "pmid": "42960598",
  "published": "2026-10-30",
  "publisher": "Taylor & Francis Group",
  "ris": "https://research.draconitic.com/paper/6eqhmrdaqnrfw.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T14:22:49Z",
      "native_id": "038df622c87442e1ace4fe3d687db875",
      "source": "doaj",
      "url": "https://doi.org/10.1080/0886022x.2026.2750582"
    },
    {
      "first_seen": "2026-11-05T12:22:38Z",
      "native_id": "PMC13726258",
      "source": "pmc",
      "url": "https://doi.org/10.1080/0886022x.2026.2750582"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Kidney Stones and Urolithiasis Treatments",
      "subfield": "general"
    }
  ],
  "title": "NADPH oxidase–associated oxidative stress and ferroptosis-related injury in calcium oxalate-exposed renal tubular epithelial cells: pharmacological evidence for PI3K/AKT involvement",
  "title_text": "NADPH oxidase–associated oxidative stress and ferroptosis-related injury in calcium oxalate-exposed renal tubular epithelial cells: pharmacological evidence for PI3K/AKT involvement",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:22:16Z",
  "url": "https://research.draconitic.com/paper/6eqhmrdaqnrfw",
  "venue": "Renal Failure",
  "versions": []
}