Ferroptosis-associated changes in transfusion-related acute lung injury in Sprague Dawley rats

Abstract Objectives Transfusion-related acute lung injury (TRALI) is a severe transfusion complication, and oxidative stress has been implicated in its pathophysiology. Whether ferroptosis-associated changes are present in TRALI remains unclear. Methods A two-hit TRALI-like model was established in Sprague Dawley (SD) rats. Animals were randomized into five groups: Control; lipopolysaccharide (LPS) (intraperitoneal, i.p., 2 mg/kg); Saline (i.p. LPS + saline); TRALI-like (i.p. LPS + human plasma); and LPS (intravenous, i.v., 5 mg/kg, positive control). Six hours after the second hit, the right lung lobe was collected for wet-to-dry (W/D) ratio assessment and haematoxylin and eosin (H&E) histology. Lung tissue glutathione (GSH), glutathione peroxidase 4 (GPX4), malondialdehyde (MDA), and prostaglandin-endoperoxide synthase 2 (PTGS2) protein expression were measured. Results The TRALI-like group exhibited a higher W/D ratio and more severe histopathological changes than the LPS (i.p.) and Saline groups, indicating an additive effect of plasma transfusion within the two-hit framework. Increased lipid peroxidation and altered antioxidant defense were observed in the TRALI-like and LPS (i.v.) groups. Conclusions Ferroptosis-associated alterations are present in this TRALI-like rat model and may be associated with lung injury. However, causal involvement cannot be concluded based solely on biomarker-based evidence.