Lipoxin A4 alleviates sepsis-induced acute liver injury by inhibiting inflammatory response and iron overload via JAK2/STAT3 signaling.

Sepsis is a systemic inflammatory response syndrome with high clinical morbidity and mortality. Acute liver injury (ALI) is a prevalent and severe complication in patients with sepsis. Studies have found that sepsis patients often have iron metabolism disorders. Lipoxin A4 (LXA4), as an inflammatory inhibitor, has an alleviating effect on many inflammation-related diseases. We aimed to examine the impact of exogenous LXA4 on Sepsis-induced acute liver injury (SALI) in an in vivo model and explore the possible mechanism involved. Through bioinformatics analysis and experimental verification, we found that LXA4 ameliorates LPS-induced ALI histological abnormalities and decreases the release of pro-inflammatory cell factors. LXA4 attenuated the content of ROS by up-regulating SOD enzymatic activity and GSH levels while reducing MDA production. Furthermore, LXA4 attenuated iron deposition by increasing FPN1 expression in ALI mice. Further studies have shown that LXA4 regulates the expression of hepcidin via the JAK2/STAT3 signaling pathway to alleviate LPS-induced sepsis. Our research findings indicate that LXA4 exerted a protective effect against iron overload and oxidative stress in ALI mice.