Dexpanthenol mitigates trauma-induced lung injury by modulating RIPK1/RIPK3/MLKL-mediated necroptosis in rats.

Thoracic trauma (TRA) triggers inflammation, oxidative stress, apoptosis, and receptor-interacting protein kinase-1 (RIPK1)/receptor-interacting protein kinase-3 (RIPK3)/mixed lineage kinase domain-like protein (MLKL)-mediated necroptosis, all of which contribute to contusion-related lung injury. Dexpanthenol (DEX) has anti-inflammatory and cytoprotective properties, yet its antinecroptotic potential in trauma-induced lung injury has not been fully elucidated. Forty male rats were randomly assigned to SHAM, TRA, TRA + DEX, and DEX groups. A 200 g cylindrical weight was dropped from a height of 100 cm, inducing TRA. Lung injury was assessed by histopathology, immunohistochemical staining for tumor necrosis factor-alpha (TNF-α) and caspase-3 (Cas-3), biochemical measurements of total oxidant status (TOS)/total antioxidant status (TAS)/oxidative stress index (OSI), and as well as mRNA expression levels of RIPK1/RIPK3/MLKL. TRA markedly increased hyperemia, edema, inflammatory infiltration, TNF-α, Cas-3, OSI, and RIPK1/RIPK3/MLKL expression (p < 0.001 for all). DEX significantly attenuated lung injury by reducing inflammatory scores, decreasing TNF-α and Cas-3 immunoreactivity, lowering OSI (p < 0.01), and suppressing RIPK1/RIPK3/MLKL gene activation (p < 0.001 for all). Although DEX did not fully normalize isolated TOS and TAS values, the OSI reduction indicates a net shift toward antioxidant balance. DEX mitigates trauma-induced lung injury through anti-inflammatory, antiapoptotic, antioxidant, and antinecroptotic mechanisms. These findings are preliminary, and dose-dependent effects and long-term outcomes should be clarified in future studies before clinical translation.