{
  "abstract": "Cyclophosphamide (CTX) is a widely used chemotherapeutic agent with well-established efficacy; however, its clinical use is limited by dose-dependent adverse effects, particularly nephrotoxicity. Protodioscin (Prot), a bioactive saponin derived from plants of the Dioscoreaceae family, has demonstrated notable antioxidant and anti-inflammatory properties. This study aimed to evaluate the protective effects of Prot against CTX-induced cytotoxicity in HEK-293 cells. Primary HEK-293 kidney cells were exposed to the IC50 concentration of CTX in the presence or absence of Prot (5 and 10 µM) for 24 hours. Cell viability was assessed using the MTT assay. Gene expression of Bax and Bcl-2 was measured by real-time PCR assay, while protein expression of Bax, cleaved caspase-3, Bcl-2, ATF6, PERK, GRP78, CHOP, p-eIF2α, p-PERK, and cleaved ATF6 were evaluated by Western blot analysis. Oxidative stress parameters, including CAT, SOD, GPx, GSH, MDA, and NO, were quantified using spectrophotometric assays, and kidney injury markers (KIM-1 and cystatin C) were measured by ELISA. Prot decreased Bax and caspase 3 expression and increased Bcl-2 expression in HEK-293 cells exposed to CTX, which was accompanied by reduced apoptosis. Treatment with 5 and 10 µM Prot significantly reduced the expression of ATF6, PERK, GRP78, CHOP, p-eIF2α, p-PERK and Cleaved- ATF6 proteins in CTX-exposed HEK-293 cells. Additionally, treatment with Prot significantly increased catalase, GPx, GSH, and SOD levels, while reducing KIM-1, cystatin C, MDA, and NO levels in HEK-293 cells subjected to CTX. These findings suggest that Prot exerts a protective role against CTX-induced renal injury in HEK-293 cells by modulating apoptotic pathways, attenuating endoplasmic reticulum stress, and improving antioxidant indices.",
  "abstract_shown": true,
  "affiliations": [
    "Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran",
    "Medicinal Plant Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran",
    "Department of Immunology, Factually of Medical Sciences, Tarbiat Modares University, Tehran, Iran",
    "Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran",
    "Stem Cells and Transgenic Technology Research Center, Shahid Chamran University of Ahvaz, Ahvaz, Iran"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ahmad Reza Ahmadi"
    },
    {
      "affs": [
        1
      ],
      "name": "Touraj Zamir Nasta"
    },
    {
      "affs": [
        2
      ],
      "name": "Ardeshir Abbasi"
    },
    {
      "affs": [
        3
      ],
      "name": "Mohammad Reza Tabandeh"
    },
    {
      "affs": [
        4
      ],
      "name": "Cyrus Jalili"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/epzgfq5ft192j.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0357227",
  "fulltext_url": null,
  "id": "epzgfq5ft192j",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0357227",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2734|Chemotherapy-induced organ toxicity mitigation"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Renal system/Kidneys"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Antioxidants"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cell processes/Cell death/Apoptosis"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cell processes/Secretory pathway/Endoplasmic reticulum"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular structures and organelles/Endoplasmic reticulum"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Oxidative stress"
    ],
    [
      "plos",
      "/Biology and life sciences/Molecular biology/Molecular biology techniques/Molecular biology assays and analysis techniques/Gene expression and vector techniques/Protein expression"
    ],
    [
      "plos",
      "/Biology and life sciences/Toxicology/Toxicity"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Renal system/Kidneys"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Toxicology/Toxicity"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pharmacology/Drugs/Cyclophosphamide"
    ],
    [
      "plos",
      "/Research and analysis methods/Molecular biology techniques/Molecular biology assays and analysis techniques/Gene expression and vector techniques/Protein expression"
    ]
  ],
  "openalex": "W7213866028",
  "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0357227&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-21",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/epzgfq5ft192j.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:43Z",
      "native_id": "10.1371/journal.pone.0357227",
      "source": "plos",
      "url": "https://doi.org/10.1371/journal.pone.0357227"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "plos:cell biology",
      "subfield": "cell-biology"
    },
    {
      "field": "medicine",
      "origin": "plos:toxicology",
      "subfield": "pharmacology-toxicology"
    },
    {
      "field": "medicine",
      "origin": "plos:anatomy",
      "subfield": "physiology"
    }
  ],
  "title": "Protodioscin mitigates cyclophosphamide-induced renal toxicity in HEK-293 cells by regulating endoplasmic reticulum stress, antioxidant defense, and apoptotic pathways",
  "title_text": "Protodioscin mitigates cyclophosphamide-induced renal toxicity in HEK-293 cells by regulating endoplasmic reticulum stress, antioxidant defense, and apoptotic pathways",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:43Z",
  "url": "https://research.draconitic.com/paper/epzgfq5ft192j",
  "venue": "PLOS One",
  "versions": []
}