Protective effect of dapagliflozin on lipopolysaccharide-induced acute lung injury via the SIRT-1/PGC-1α pathway
Molecular Biology Reports, cilt.52, sa.1, 2025 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 52 Sayı: 1
- Basım Tarihi: 2025
- Doi Numarası: 10.1007/s11033-025-10267-y
- Dergi Adı: Molecular Biology Reports
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, Veterinary Science Database
- Anahtar Kelimeler: Acute lung injury, Apoptosis, ARDS, Dapagliflozin, Inflammation
- Süleyman Demirel Üniversitesi Adresli: Evet
Özet
Background: Acute systemic inflammation affects many organs and it occurs in a wide range of conditions such as acute lung injury (ALI). Inflammation-triggered oxidative pathways together with the caspase activation seen in ALI, result in apoptosis. Dapagliflozin (DPG) is an agent that is known to have oxidative stress-reducing and anti-inflammatory effects in many tissues. Methods and results: Thirty-two Wistar albino rats were divided into four groups: control, lipopolysaccharide (LPS) (5 mg/kg), LPS + DPG (10 mg/kg) and DPG. DPG was orally administered for five consecutive days LPS was intraperitoneally applied in a single dose on the fifth day and the animals were euthanized six hours after the last drug administration. Lung tissues were harvested. In addition to hematoxylin-eosin staining, caspase-3 (Cas-3) and tumor necrosis factor alpha (TNF-α) immunostainings were conducted. While total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) were examined biochemically, Sirtuin-1 (SIRT-1), Peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α), B-cell lymphoma 2 (Bcl-2), and Bcl-2 associated X protein (Bax) were examined by PCR. Histopathological analysis revealed hyperemia, edema, inflammatory cell infiltration, and epithelial cell loss. In LPS group, Cas-3, TNF-α, TOS, OSI, and Bax values increased whereas SIRT-1, PGC-1α, and Bcl-2 values decreased. All these changes were restored with DPG treatment. Conclusion: DPG exhibited protective effects against inflammation, oxidative stress, and subsequent apoptosis observed in systemic inflammation-induced ALI likely through SIRT-1/ PGC-1α pathway.