Dapansutrile Mitigates DHT-Induced Polycystic Ovary Syndrome by Suppressing NLRP3 Inflammasome and TLR4/NF-κB Signaling

AKBAŞ B., DİNÇ G., AKBAŞ A., Ercan G., Aygün H., Erbas O.

Bratislava Medical Journal, 2026 (SCI-Expanded, Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1007/s44411-026-00514-4
  • Dergi Adı: Bratislava Medical Journal
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Anahtar Kelimeler: Anti-Müllerian hormone, Dapansutrile, IGF-1, Inflammation, NLRP3 inflammasome, Polycystic ovary syndrome
  • Karadeniz Teknik Üniversitesi Adresli: Evet

Özet

This study investigated the therapeutic effects of Dapansutrile, a selective NLRP3 inflammasome inhibitor, on ovarian dysfunction in a dihydrotestosterone (DHT)-induced polycystic ovary syndrome (PCOS) rat model. Thirty adult female Wistar rats were allocated to control, PCOS + saline, and PCOS + Dapansutrile groups. PCOS was induced by subcutaneous DHT pellet implantation, followed by 28 days of intraperitoneal saline or Dapansutrile (100 mg/kg/day). Ovarian histology (follicle counts, fibrosis) and biochemical parameters (hormones, inflammatory and oxidative markers) were assessed. DHT exposure disrupted folliculogenesis, reducing primary (P < 0.001), secondary (P < 0.001), and tertiary follicles (P = 0.004), and markedly increased fibrosis (P < 0.001). Dapansutrile significantly enhanced primary (P < 0.01) secondary (P < 0.05) and tertiary follicle counts (P < 0.05), alleviated ovarian fibrosis (P < 0.001). Biochemically, PCOS rats exhibited elevated AMH, IGF-1, TNF-α, TLR4, MyD88, NF-κB, NLRP3, caspase-1, IL-1β, IL-18, and TGF-β1, alongside depleted ovarian GSH. Treatment with Dapansutrile attenuated inflammatory and fibrotic markers, elevated GSH, and decreased AMH and IGF-1, without altering insulin levels. Collectively, these findings provide the first evidence that Dapansutrile alleviates PCOS-induced ovarian dysfunction by suppressing inflammasome-driven inflammation, oxidative stress, and fibrosis, thereby improving follicular maturation and reducing stromal fibrosis in a hyperandrogenic PCOS model.