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

Shujun Sun; Li Wang; Jiamei Wang; Rui Chen; Shuaijie Pei; Shanglong Yao; Yun Lin; Chengye Yao; Haifa Xia

doi:10.1016/j.heliyon.2023.e21883

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

Heliyon. 2023 Nov 3;9(11):e21883. doi: 10.1016/j.heliyon.2023.e21883. eCollection 2023 Nov.

Authors

Shujun Sun^{1

2

3}, Li Wang^{1

2

3}, Jiamei Wang⁴, Rui Chen^{1

2

3}, Shuaijie Pei^{1

2

3}, Shanglong Yao^{1

2

3}, Yun Lin^{1

2

3}, Chengye Yao⁵, Haifa Xia^{1

2

3}

Affiliations

¹ Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
² Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
³ Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, China.
⁴ Wuhan Institute of Biological Products Co. Ltd, Wuhan, 430022, China.
⁵ Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Abstract

Aims: The treatment of sepsis remains challenging and the liver is a non-neglectful target of sepsis-induced 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 low-dose MaR1 (0.5 ng, 200 μL) or high-dose MaR1 (1 ng, 200 μL) or sterile normal saline (NS) (200 μL) 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 anti-inflammatory effects by decreasing the expression of pro-inflammatory molecules (TNF-α, IL-6 and IL-1β), bacterial load, and neutrophil infiltration and increasing the expression of anti-inflammatory 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.

Keywords: Cecal ligation and puncture (CLP); Inflammatory; Maresin1 (MaR1); NF-κB/Stat3/MAPK signaling pathways; Sepsis-induced acute liver injury (SI-ALI).