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Characterization of changes in plasma and tissue oxylipin levels in LPS and CLP induced murine sepsis

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Abstract

Objective

The present study aimed to comprehensively investigate the changes in oxylipins during murine sepsis induced by lipopolysaccharide (LPS) or cecal ligation and puncture (CLP).

Methods

Twenty-four hours after induction of sepsis in male C57BL/6 mice by LPS or CLP, plasma and liver, lung, kidney and heart tissues were sampled. Oxylipin levels in plasma and tissue were quantified by means of LC–MS. Moreover, clinical chemistry parameters were determined in plasma and interleukin levels (MCP-1 and IL-6) were determined in kidney and liver.

Results

Elevation of liver function plasma parameters at 24 h revealed that both models were successful in the induction of sepsis. LPS induced sepsis resulted in a dramatic increase of plasma PGE2 (2,100 % change in comparison to control) and other cyclooxygenase metabolites, whereas this effect was less pronounced in CLP induced sepsis (97 % increase of PGE2). Plasma epoxy-fatty acids (FAs) and hydroxy-FAs and most of the dihydroxy-FAs were elevated in both models of sepsis. Changes of tissue oxylipin concentrations were organ dependent. Only few changes were detected in the lung and liver tissue, epoxy-FAs were elevated in the kidney. In the heart tissue a trend towards lower levels of hydroxy-FAs and epoxy-FAs was observed.

Conclusion

Both murine models of sepsis are characterized by changes of oxylipins formed in all branches of the arachidonic acid (AA) cascade. The more pronounced effects in the LPS model make this model more suitable for the investigation of the AA cascade and its pharmacological modulation in sepsis.

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Acknowledgments

Our work is supported by Fonds der Chemischen Industrie, the European Union (Marie Curie Career Integration Grant CIG 293536) and the German Research Foundation (Grant SCHE 1801). We thank Martina Ackermann and Herle Chlebusch for excellent technical assistance.

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Authors and Affiliations

  1. Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hannover, Bischofsholer Damm 15, 30173, Hannover, Germany

    Ina Willenberg, Katharina Rund & Nils Helge Schebb

  2. Department of Nephrology, Hannover Medical School, Hannover, Germany

    Song Rong, Nelli Shushakova & Faikah Gueler

  3. The Transplantation Center of the Affiliated Hospital, Zunyi Medical College, Zunyi, China

    Song Rong

  4. Phenos GmbH, Hannover, Germany

    Nelli Shushakova & Faikah Gueler

  5. Institute of Food Chemistry, University of Wuppertal, Wuppertal, Germany

    Nils Helge Schebb

Authors
  1. Ina Willenberg
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  2. Katharina Rund
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  3. Song Rong
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  4. Nelli Shushakova
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  5. Faikah Gueler
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  6. Nils Helge Schebb
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Correspondence to Nils Helge Schebb.

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Responsible Editor: John Di Battista.

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Willenberg, I., Rund, K., Rong, S. et al. Characterization of changes in plasma and tissue oxylipin levels in LPS and CLP induced murine sepsis. Inflamm. Res. 65, 133–142 (2016). https://doi.org/10.1007/s00011-015-0897-7

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  • DOI: https://doi.org/10.1007/s00011-015-0897-7

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