10-epi-Protectin DX and Resolvin D5n-3 DPA Attenuate Multi-Organ Inflammatory Injury in an LPS-Induced Murine Endotoxemia Model

Sepsis is a life-threatening syndrome driven by dysregulated immune activation and multi-organ dysfunction, with limited effective therapies. Oxylipins are endogenous lipid mediators that promote the resolution of inflammation and tissue repair, yet their therapeutic potential in systemic inflammatory diseases remains incompletely understood. In this study, we evaluated the effects of two oxylipins, 10-epi-Protectin DX (10-epi-PDX) and Resolvin D5n-3 DPA (RvD5n-3 DPA), in a lipopolysaccharide (LPS)-induced murine endotoxemia model. Given that this model recapitulates key features of systemic inflammation and multi-organ injury relevant to sepsis-associated conditions, oxylipin effects were assessed across major organs implicated in systemic inflammatory pathology. Administration of either oxylipin significantly reduced systemic tissue injury and inflammatory damage in the lungs, kidneys, and liver. These protective effects were accompanied by suppression of inflammatory responses and marked improvements in histopathological outcomes. These findings indicate that 10-epi-PDX and RvD5n-3 DPA possess organ-protective, anti-inflammatory properties in endotoxemia and support further investigation of their potential as therapeutic candidates for limiting systemic inflammatory injury.