Maresin1 prevents sepsis-induced acute liver injury by suppressing NF-KB/Stat3/MAPK pathways, mitigating inflammation

Aims: The treatment of sepsis remains challenging and the liver is a non-neglectful target of sepsisinduced injury. Uncontrolled inflammatory responses exert a central role in the pathophysiological process of sepsis-induced acute liver injury (SI-ALI). Maresin1 (MaR1) is a derivative of omega-3 docosahexaenoic acid (DHA), which has been shown to have anti-inflammatory effects and is effective in a variety of sepsis-related diseases. This study aimed to determine the effect of MaR1 on cecal ligation and puncture (CLP)-caused SI-ALI and explore its possible mechanisms. Main methods: Mice were subjected to CLP, and then intravenously injected via tail vein with lowdose MaR1 (0.5 ng, 200 mu L) or high-dose MaR1 (1 ng, 200 mu L) or sterile normal saline (NS) (200 mu L) 1 h later. Then, the survival rate, body weight change, liver function, bacterial load, neutrophil infiltration, and inflammatory cytokines were detected. Results: MaR1 significantly increased the 7-day survival rate and reduced the bacterial load in peritoneal lavage fluid and blood in a dose-dependent manner in mice with SI-ALI. Treatment with MaR1 could also restore the function of the liver in septic mice. Besides, MaR1 exerted antiinflammatory effects by decreasing the expression of pro-inflammatory molecules (TNF-a, IL-6 and IL-1(i), bacterial load, and neutrophil infiltration and increasing the expression of antiinflammatory molecules (IL-10). Significance: Our experimental results showed that MaR1 alleviated liver injury induced by sepsis. This work highlighted a potential clinic use of MaR1 in treating acute inflammation of SI-ALI, but also provided new insight into the underlying molecular mechanism.