Comparative Protective Effects of ATP and TPP Against Olaparib-Induced Ovarian Injury in Rats: Insights from Biochemical Parameters, Histopathology, and IRE1α, Cleaved Caspase-3, LC3B, and NF-κB p65 Double Immunofluorescence
Drug Design, Development and Therapy, cilt.20, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 20
- Basım Tarihi: 2026
- Doi Numarası: 10.2147/dddt.s634516
- Dergi Adı: Drug Design, Development and Therapy
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, MEDLINE, Directory of Open Access Journals, Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest)
- Anahtar Kelimeler: adenosine triphosphate, apoptosis, autophagy, endoplasmic reticulum stress, inflammation, olaparib, ovarian diseases/chemically induced, oxidative stress, rats, thiamine pyrophosphate
- Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
- Sivas Cumhuriyet Üniversitesi Adresli: Evet
Özet
Background: Olaparib is a poly(ADP-ribose) polymerase (PARP) inhibitor used to treat several malignancies. Previous studies have reported that olaparib may induce ovarian injury by elevating reactive oxygen species and impairing cellular energy homeostasis. ATP is a central regulator of intracellular energy balance and antioxidant defense, whereas thiamine pyrophosphate (TPP), the active form of vitamin B1, supports ATP biosynthesis and possesses antioxidant and anti-inflammatory properties. This study compared the protective effects of ATP and TPP against olaparib-induced ovarian injury in rats. Methods: Twenty-four female Wistar albino rats were randomly assigned to four groups (n=6 each): healthy control (HG), olaparib-only (OLP), ATP plus olaparib (ATOL), and TPP plus olaparib (TPOL). Olaparib (100 mg/kg, orally, twice daily), ATP (5 mg/kg, intraperitoneally, once daily), and TPP (25 mg/kg, intraperitoneally, once daily) were administered for 14 consecutive days. Ovarian tissue levels of oxidant (MDA), antioxidants (tGSH, SOD, CAT), and pro-inflammatory cytokine (IL-6) were determined. Tissue specimens underwent histopathological (follicular and parenchymal degeneration) and double immunofluorescence analyses (IRE1α, cleaved Caspase-3, LC3B, and NF-κB p65 immunopositivity). Results: Olaparib significantly increased oxidant and pro-inflammatory cytokine levels and decreased antioxidant levels. Histopathology revealed severe follicular and parenchymal degeneration, and immunofluorescence analysis showed significantly increased IRE1α, cleaved Caspase-3, LC3B, and NF-κB p65 immunopositivity. Both ATP and TPP pre-treatment significantly attenuated olaparib-induced oxidative stress, inflammatory responses, histopathological injury, and cellular stress marker immunopositivity. ATP demonstrated a more pronounced protective effect than TPP, particularly regarding follicular degeneration suppression and LC3B and NF-κB p65 immunopositivity. Conclusion: Olaparib induced ovarian injury accompanied by oxidative stress, cytokine-mediated inflammation, IRE1α-related endoplasmic reticulum stress, cleaved Caspase-3-related apoptosis, LC3B-related autophagy, and NF-κB-related inflammatory signaling. Both ATP and TPP attenuated olaparib-associated injury, with greater effects for ATP. These findings suggest that maintenance of cellular energy homeostasis may represent a promising strategy for attenuating PARP inhibitor-induced ovarian injury.