Abstract
Maresin1 (MaR1), a new anti-inflammatory and proresolving lipid mediator, has been proven to exert organ-protective effects in septic animal models. However, the potential mechanisms are still not fully elucidated. In this study, we sought to explore the impact of MaR1 on metabolic dysfunction in cecal ligation and puncture- (CLP-) induced septic mice. We found that MaR1 significantly increased the overall survival rate and attenuated lung and liver injuries in septic mice. In addition, MaR1 markedly reduced the levels of proinflammatory cytokines (TNF-α and IL-6) and alleviated mitochondrial damage. Based on a 1H NMR-based metabolomics analysis, CLP-induced septic mice had increased levels of acetate, pyruvate, and lactate in serum and decreased levels of alanine, aspartate, glutamate, and fumarate in lungs. However, these metabolic disorders, mainly involving energy and amino acid metabolism, can be recovered by MaR1 treatment. Therefore, our results suggest that the protective effects of MaR1 on sepsis could be related to the recovery of metabolic dysfunction and the alleviation of inflammation and mitochondrial damage.
Highlights
Sepsis is a life-threatening clinical syndrome characterized by multiple organ dysfunctions due to uncontrolled host inflammatory responses towards infection or injury [1]
Our results show that the treatment of MaR1 markedly increased the survival rate and alleviated lung and liver injury in cecal ligation and puncture- (CLP-)induced septic mice
We investigated metabolic changes in CLP-induced septic mice after MaR1 treatment using NMR-based metabolomics and found two main metabolic pathways recovered by MaR1, including pyruvate metabolism and alanine, aspartate, and glutamate metabolism
Summary
Sepsis is a life-threatening clinical syndrome characterized by multiple organ dysfunctions due to uncontrolled host inflammatory responses towards infection or injury [1]. Sepsis is becoming a leading cause of morbidity and mortality globally, because to date no efficient antisepsis therapy is available [2]. It is, important to discover specific and effective drugs to treat sepsis. A recent research showed that MaR1 mitigated the lipopolysaccharide (LPS) level and enhanced the bacteria clearance in septic mice [6]. Our previous study indicated that MaR1 improved alveolar fluid clearance via upregulation of epithelial sodium channel expression in an LPS-induced acute lung injury model [7]. The potential mechanisms of MaR1 for sepsis treatment are still far from being fully understood
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