Protective effect of dapagliflozin on lipopolysaccharide-induced acute lung injury via the SIRT-1/PGC-1α pathway
Savran M. Akin S.E. Camas H.E. Ilhan I. Arlioglu M. Zeynalov T. Ozmen O. Ozcan M.S.
December 2025Springer Science and Business Media B.V.
Molecular Biology Reports
2025#52Issue 1
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.
Acute lung injury , Apoptosis , ARDS , Dapagliflozin , Inflammation
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Department of Pharmacology, Faculty of Medicine, Suleyman Demirel University, Isparta, Kazakhstan
Department of Thoracic Surgery, Faculty of Medicine, Suleyman Demirel University, Isparta, Kazakhstan
Department of Biochemistry, Faculty of Medicine, Suleyman Demirel University, Isparta, Kazakhstan
Faculty of Medicine, Suleyman Demirel University, Isparta, Kazakhstan
Department of Pathology, Faculty of Veterinary, Burdur Mehmet Akif Ersoy University, Burdur, Türkiye
Department of Anesthesiology and Reanimation, Faculty of Medicine, Suleyman Demirel University, Isparta, Kazakhstan
Department of Pharmacology
Department of Thoracic Surgery
Department of Biochemistry
Faculty of Medicine
Department of Pathology
Department of Anesthesiology and Reanimation
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