{
  "abstract": "Polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic disorder characterized by ovarian dysfunction, hormonal imbalance, and emerging ferroptosis-related abnormalities. This study investigated the effects of alpha-lipoic acid (ALA), saxagliptin (Saxa), and their combination in a letrozole-induced PCOS model, with focus on the ovarian FGF21/NOX4–NRF2/HO-1 and ferroptosis-related pathways. PCOS was induced in female rats by oral letrozole administration for 21 days. Rats were allocated into control, PCOS, ALA, Saxa, and ALA/Saxa groups, followed by 14 days of treatment. Body weight, ovarian index, ovarian histopathology, reproductive hormones, oxidative stress markers, ovarian FGF21 and NOX4 expression, NRF2/HO-1 signaling, and ferroptosis-related markers, including Fe+2, GPX4, and SLC7A11, were assessed. Letrozole induced weight gain, ovarian hypertrophy, follicular disruption, endocrine imbalance, and ferroptosis-related alterations, marked by increased ROS, MDA, Fe2+, and NOX4, alongside reduced FGF21, NRF2/HO-1, GPX4, and SLC7A11. ALA or Saxa attenuated these alterations, whereas ALA/Saxa produced greater improvements in ovarian morphology, hormonal status, redox homeostasis, and ferroptosis-related markers. These effects were associated with FGF21 upregulation, NOX4 suppression, enhanced NRF2/HO-1 signaling, and preservation of GPX4 and SLC7A11. In conclusion, ALA/Saxa therapy markedly ameliorated letrozole-induced PCOS in rats, accompanied by restoration of ovarian FGF21/NOX4 homeostasis, associated with enhancement of NRF2/HO-1 antioxidant responses, and attenuation of ferroptosis-related alterations.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmacology and Biochemistry (Biochemistry), Faculty of Pharmacy, Horus University-Egypt, New Damietta 34518, Egypt",
    "Department of Pharmacology and Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, Egypt",
    "Department of Pharmacology, Faculty of Veterinary Medicine, Assiut University, Assiut 71526, Egypt",
    "Department of Pharmacology, School of Veterinary Medicine, Badr University in Assiut (BUA), Naser City 11829, Egypt",
    "Department of Histology, Faculty of Medicine (Boys), Al-Azhar University, Cairo 11884, Egypt",
    "Department of Histology, General Medicine Practice Program, Batterjee Medical College, Jeddah 21442, Saudi Arabia",
    "Department of Medical Physiology, Faculty of Medicine, Cairo University, Cairo 12613, Egypt",
    "Department of Medical Physiology, General Medicine Practice Program, Batterjee Medical College, Jeddah 21442, Saudi Arabia"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Eman H. Yousef",
      "orcid": "0000-0001-8964-458X"
    },
    {
      "affs": [
        1
      ],
      "name": "Mona H. Zohny",
      "orcid": "0009-0008-2099-5793"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Ebtsam S. Abdel-lah"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Mostafa E. Metawee"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Hader I. Sakr"
    },
    {
      "affs": [
        1
      ],
      "name": "Mohamed M. Salama",
      "orcid": "0000-0002-2907-5626"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/770k09zgxmdmf.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27219779",
  "fulltext_url": null,
  "id": "770k09zgxmdmf",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/21/9779",
  "language": null,
  "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": [],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-30",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/770k09zgxmdmf.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:54Z",
      "native_id": "10.3390/ijms27219779",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/21/9779"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "issn:1422-0067",
      "subfield": "general"
    }
  ],
  "title": "Alpha-Lipoic Acid and Saxagliptin Attenuate Ferroptosis-Related Ovarian Injury and Modulate FGF21/NOX4–NRF2/HO-1 Signaling in Letrozole-Induced Polycystic Ovary Syndrome",
  "title_text": "Alpha-Lipoic Acid and Saxagliptin Attenuate Ferroptosis-Related Ovarian Injury and Modulate FGF21/NOX4–NRF2/HO-1 Signaling in Letrozole-Induced Polycystic Ovary Syndrome",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T00:20:52Z",
  "url": "https://research.draconitic.com/paper/770k09zgxmdmf",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}