| Title |
Simvastatin and a Plant Galactolipid Protect Animals from Septic Shock by Regulating Oxylipin Mediator Dynamics through the MAPK-cPLA2 Signaling Pathway
|
|---|---|
| Published in |
Molecular Medicine, December 2015
|
| DOI | 10.2119/molmed.2015.00082 |
| Pubmed ID | |
| Authors |
Maria Karmella Apaya, Chih-Yu Lin, Ching-Yi Chiou, Chung-Chih Yang, Chen-Yun Ting, Lie-Fen Shyur |
| Abstract |
Sepsis remains a major medical issue despite decades of research. Identification of important inflammatory cascades and key molecular mediators are crucial for developing intervention and prevention strategies. In this study, we conducted a comparative oxylipin metabolomics study to gain a comprehensive picture of lipid mediator dynamics during the initial hyper-inflammatory phase of sepsis, and demonstrated, in parallel, the efficacy of simvastatin and plant galactolipid, 1,2-di-O-α-linolenoyl-3-O-β-galactopyranosyl-sn-glycerol (dLGG) in the homeostatic regulation of the oxylipin metabolome using a lipopolysaccharide (LPS)-induced sepsis C57BL/6J mouse model. LPS increased the systemic and organ levels of pro-inflammatory metabolites of linoleic acid including leukotoxin diols, i.e., 9,10-DHOME, 12,13-DHOME, and octadecadienoic acids, i.e., 9-HODE and 13-HODE; and arachidonic acid-derived prostanoid, PGE2, and hydroxyeicosatetraenoic acids, i.e., 8, 12- and 15-HETE. Treatment with either compound decreased the levels of pro-inflammatory metabolites and elevated pro-resolution lipoxin A4, 5(6)-EET, 11(12)-EET and 15-deoxy-PGJ2. dLGG and simvastatin ameliorated the effects of LPS-induced MAPK-dependent activation of cPLA2, cyclooxygenase-2, lipoxygenase, cytochrome P450, and/or epoxide hydrolase, lowered systemic TNF-α and IL-6 levels and aminotransferase activities and decreased organ-specific infiltration of inflammatory leukocytes and macrophages, and septic shock-induced multiple organ damage. Furthermore, both dLGG and simvastatin increased the survival rates in the cecal ligation and puncture (CLP) sepsis model. This study provides new insights into the role of oxylipins in sepsis pathogenesis and highlights the potential of simvastatin and dLGG in sepsis therapy and prevention. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 17 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Netherlands | 1 | 6% |
| Unknown | 16 | 94% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 4 | 24% |
| Student > Ph. D. Student | 3 | 18% |
| Student > Master | 2 | 12% |
| Professor > Associate Professor | 1 | 6% |
| Unspecified | 1 | 6% |
| Other | 0 | 0% |
| Unknown | 6 | 35% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 4 | 24% |
| Immunology and Microbiology | 2 | 12% |
| Unspecified | 1 | 6% |
| Agricultural and Biological Sciences | 1 | 6% |
| Business, Management and Accounting | 1 | 6% |
| Other | 2 | 12% |
| Unknown | 6 | 35% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 December 2015.
All research outputs
#18,433,196
of 22,836,570 outputs
Outputs from Molecular Medicine
#913
of 1,139 outputs
Outputs of similar age
#281,474
of 389,737 outputs
Outputs of similar age from Molecular Medicine
#10
of 21 outputs
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