Sodium Phenylbutyrate Ameliorates Ovariectomy-Induced Bone Loss in Rats

AKBAŞ B., DİNÇ G., AKBAŞ A., Hacım N. A., Ercan G., Aygün H., ...Daha Fazla

Medicina (Lithuania), cilt.61, sa.11, 2025 (SCI-Expanded, Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 61 Sayı: 11
  • Basım Tarihi: 2025
  • Doi Numarası: 10.3390/medicina61112016
  • Dergi Adı: Medicina (Lithuania)
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Directory of Open Access Journals
  • Anahtar Kelimeler: bone loss, cytokines, osteoporosis, ovariectomy, oxidative stress, sodium phenylbutyrate
  • Karadeniz Teknik Üniversitesi Adresli: Evet

Özet

Background and Objectives: Estrogen deficiency after menopause accelerates bone loss through oxidative stress and inflammatory cytokines. Sodium phenylbutyrate (SP), a histone deacetylase inhibitor, exhibits antioxidative and anti-inflammatory effects, but its impact on postmenopausal osteoporosis remains unclear. Materials and Methods: Thirty female Wistar rats were divided into control, ovariectomy (OVX), and OVX+SPB groups (n = 10 each). After 12 weeks, bone mineral density (BMD), histomorphometry, bone marrow biomarkers (MDA, TNF-α, IL-6, RANKL), and plasma Cathepsin K were evaluated. Results: OVX induced trabecular deterioration with reduced number, area, and thickness (all p < 0.001), increased separation (p < 0.001), and decreased femoral and lumbar BMD (p < 0.001). SPB significantly improved these indices (TN, p < 0.05; TA, p < 0.01; TH, p < 0.05; femoral BMD, p < 0.05; lumbar BMD, p < 0.001; TS, p = 0.001). OVX elevated MDA, TNF-α, IL-6, RANKL, and Cathepsin K (all p < 0.001), which were significantly reduced by SPB (MDA, p < 0.001; TNF-α, p < 0.01; IL-6, p < 0.01; RANKL, p < 0.001; Cathepsin K, p < 0.001). Conclusions: SPB mitigates OVX-induced oxidative stress, inflammatory cytokine release, and osteoclast-mediated resorption, resulting in partial but significant improvements across biochemical, structural, and histomorphometric parameters in estrogen-deficient rats. Given its established clinical safety profile, SPB emerges as a cost-effective candidate for repurposing in postmenopausal osteoporosis, warranting further translational and clinical studies.