Investigating the effects of dexmedetomidine in cecal ligation and puncture‑induced septic rats

Sepsis is a leading cause of mortality, and ferroptosis has been implicated in sepsis-associated organ injury. Dexmedetomidine (DEX), an α2-adrenergic agonist with anti-inflammatory properties, may modulate this process. We examined whether DEX protects against cecal ligation and puncture (CLP)– induced septic lung injury and alters ferroptosis-associated markers in rats. Thirty-two female Wistar rats were randomized to sham, CLP, and CLP pretreated with DEX (30–50 µg/kg, intraperitoneally, 30 min before CLP) groups ( n = 8 each) and euthanized 16 h after surgery. Lung injury was assessed histopathologically; ferroptosis and inflammation were evaluated by serum ELISA (MDA, ferritin, ACSL4, HO-1, IL-18, SLC7A11), immunohistochemistry (GPX4, TFRC), and immunofluorescence (AQP5, IL-1β). CLP produced severe lung injury, increased MDA, ferritin, ACSL4, HO-1, IL-18, TFRC, and IL-1β, and decreased SLC7A11, GPX4, and AQP5. DEX attenuated histopathological injury, with an ordered dose trend for the primary outcome (interstitial pneumonia; p < 0.001), and shifted these biomarkers toward sham; serum markers differed between doses, and normalization remained partial. These findings indicate that DEX mitigates CLP-induced lung injury, associated with reduced lipid peroxidation, iron-handling, and inflammatory markers, and partial restoration of SLC7A11 and GPX4; whether ferroptosis inhibition mediates this protection requires confirmation with ferroptosis inhibitors and inducers.