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Background <p>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.</p> Methods and results <p>Thirty-two Wistar albino rats were divided into four groups: control, lipopolysaccharide (LPS) (5&#xa0;mg/kg), LPS + DPG (10&#xa0;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.</p> Conclusion <p>DPG exhibited protective effects against inflammation, oxidative stress, and subsequent apoptosis observed in systemic inflammation-induced ALI likely through SIRT-1/ PGC-1α pathway.</p>

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Protective effect of dapagliflozin on lipopolysaccharide-induced acute lung injury via the SIRT-1/PGC-1α pathway

  • 期刊论文

  • 发表日期：

    2025年1月29日

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  • Mehtap Savran,
  • Suleyman Emre Akin,
  • Hasan Ekrem Camas,
  • Ilter Ilhan,
  • Melih Arlioglu,
  • Toghrul Zeynalov,
  • Ozlem Ozmen,
  • Mustafa Soner Ozcan

摘要

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.