Background/Objectives: Sepsis is a life-threatening syndrome arising from a dysregulated host response to infection, frequently leading to multiple organ dysfunction, with the lungs being among the most severely affected organs. Oxidative stress, inflammation, apoptosis, and DNA damage play key roles in the pathogenesis of sepsis-induced acute lung injury (ALI). Beyond its lipid-lowering effects, rosuvastatin possesses anti-inflammatory and antioxidant properties that may confer protective effects in sepsis. This study was designed to investigate the dose-dependent prophylactic efficacy of rosuvastatin in mitigating pulmonary damage in rats with cecal ligation and puncture (CLP)-induced sepsis. Methods: Sprague–Dawley rats were randomly divided into six groups: Sham, Sham + rosuvastatin (10 mg/kg), Sham + rosuvastatin (20 mg/kg), CLP, CLP + rosuvastatin (10 mg/kg), and CLP + rosuvastatin (20 mg/kg). Rosuvastatin was administered via oral gavage 4 h before the surgical procedures in the experimental groups. All animals were sacrificed 16 h following surgical procedures. Lung tissues were analyzed for biochemical markers, including malondialdehyde (MDA) and reduced glutathione (GSH), as well as histopathological changes and immunohistochemical expression of NF-κB/p65, caspase-3, and 8-OHdG. Results: CLP-induced sepsis significantly increased MDA levels while decreasing GSH levels, indicating enhanced oxidative stress. Rosuvastatin treatment significantly reversed these changes. Histopathological analysis revealed marked lung injury in the CLP group, including alveolar inflammation, interstitial inflammation, vascular congestion, and increased alveolar septal thickness, all of which were significantly reduced following rosuvastatin administration. Immunohistochemical findings demonstrated increased expression of NF-κB/p65, caspase-3, and 8-OHdG in the CLP group, whereas rosuvastatin significantly attenuated these expressions. No significant difference in prophylactic efficacy was observed between the 10 mg/kg and 20 mg/kg doses of rosuvastatin. Conclusions: Rosuvastatin demonstrated a protective effect against sepsis-induced pulmonary damage by reducing oxidative stress, inflammation, apoptosis, and DNA damage. These findings suggest that rosuvastatin may have prophylactic potential in sepsis; however, further support is needed from investigations of cellular pathways in different mechanistic directions.

Background/Objectives: Sepsis is a life-threatening condition characterized by a dysregulated host immune response, frequently leading to multiple organ dysfunction, with the lungs being among the most severely affected organs. Oxidative stress, inflammation, apoptosis, and DNA damage play key roles in the pathogenesis of sepsis-induced acute lung injury (ALI). Beyond its lipid-lowering effects, rosuvastatin possesses anti-inflammatory and antioxidant properties that may confer protective effects in sepsis. This study aimed to evaluate the dose-dependent effect of rosuvastatin against pulmonary damage in an experimental model of sepsis induced by cecal ligation and puncture (CLP). Methods: Sprague–Dawley rats were randomly divided into six groups: Sham, Sham + rosuvastatin (10 mg/kg), Sham + rosuvastatin (20 mg/kg), CLP, CLP + rosuvastatin (10 mg/kg), and CLP + rosuvastatin (20 mg/kg). Rosuvastatin was administered via oral gavage before 4 hours the CLP procedure in the experimental groups. All rats were euthanized 16 hours after induction of CLP. Lung tissues were analyzed for biochemical markers, including malondialdehyde (MDA) and reduced glutathione (GSH), as well as histopathological changes and immunohistochemical expression of NF-κB/p65, caspase-3, and 8-OHdG. Results: CLP-induced sepsis significantly increased MDA levels while decreasing GSH levels, indicating enhanced oxidative stress. Rosuvastatin treatment significantly reversed these changes. Histopathological analysis revealed marked lung injury in the CLP group, including alveolar inflammation, interstitial inflammation, vascular congestion, and increased alveolar septal thickness, all of which were significantly reduced following rosuvastatin administration. Immunohistochemical findings demonstrated increased expression of NF-κB/p65, caspase-3, and 8-OHdG in the CLP group, whereas rosuvastatin significantly attenuated these expressions. No significant differences were observed between the two rosuvastatin doses. Conclusion: Rosuvastatin exerts significant protective effects against sepsis-induced lung injury by reducing oxidative stress, inflammation, apoptosis, and DNA damage. These findings suggest that rosuvastatin may have therapeutic potential in the management of sepsis-associated pulmonary injury, although further studies are required to confirm its clinical applicability.