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Inflammation

, Volume 42, Issue 2, pp 598–605 | Cite as

Protective Effects of Sodium Pyruvate during Systemic Inflammation Limited to the Correction of Metabolic Acidosis

  • Katharina Effenberger-NeidnichtEmail author
  • Stephan Brauckmann
  • Johannes Jägers
  • Vivien Patyk
  • Indra Naemi Waack
  • Michael Kirsch
ORIGINAL ARTICLE

Abstract

Protective effects by exogenous sodium pyruvate already have been described in various experimental models of injury, among others during intestinal ischemia-reperfusion injury, hemorrhagic shock, and shock secondary to systemic inflammation (endotoxemic shock). Low doses of sodium pyruvate reduced signs of inflammation, enhanced systemic blood pressure, and ameliorated metabolic acidosis when administered in a prophylactic manner during endotoxemic shock. In the present study, we investigated whether low-dosed infusions of sodium pyruvate exhibited beneficial effects when applied therapeutically after the induction of systemic inflammation. Lipopolysaccharide was infused at a rate of 0.5 mg/kg × h over a period of 360 min to induce systemic inflammation in male Wistar rats. Sodium pyruvate (single dose 50 mg/kg × 15 min) was administered intravenously 180 and 270 min after starting of the lipopolysaccharide infusion. Systemic/vital parameters (e.g., systemic blood pressure and breathing rate) and blood/plasma parameters (e.g., acid-base parameters; electrolytes; glucose and lactate concentration; hemolysis; aminotransferase activities; and parameters of coagulation) were determined in regular intervals. Lipopolysaccharide infusion led to metabolic acidosis, hypoglycemia, electrolyte as well as hemostatic disturbances, and hemolysis. Except for the acid-base status (amelioration of metabolic acidosis) and the plasma chloride concentration (reduction of hyperchloremia), the additional infusion of sodium pyruvate failed in significantly improving lipopolysaccharide-dependent alterations (e.g. vital, blood and plasma parameters). Protective effects of a delayed administration of the metabolizable anion pyruvate during systemic inflammation, hence, are limited to its function as alkalizer to counteract metabolic acidosis.

KEY WORDS

lipopolysaccharide sepsis metabolism acidosis intestine pyruvate 

Notes

Acknowledgments

The authors thank Mrs. Eva Hillen and Mr. Falk Kähler for their excellent technical assistance.

References

  1. 1.
    McKechnie, S., and T. Walsh. 2018. Metabolic response to injury, fluid and electrolyte balance and shock. In Principles and practice of surgery, ed. O.J. Garden and R.W. Parks, 3–28. Edinburgh: Elsevier.Google Scholar
  2. 2.
    Wang, Y., Y. Huang, J. Yang, F.Q. Zhou, L. Zhao, and H. Zhou. 2018. Pyruvtae is a prospective alkalizer to correct hypoxic lactic acidosis. Military Medical Research 5: 13.CrossRefGoogle Scholar
  3. 3.
    Jägers, J., S. Brauckmann, M. Kirsch, and K. Effenberger-Neidnicht. 2017. Moderate glucose supply reduces hemolysis during systemic inflammation. Journal of Inflammation Research 11: 87–94.CrossRefGoogle Scholar
  4. 4.
    Mallet, R.T., J. Sun, E.M. Knott, A.B. Sharma, and A.H. Olivencia-Yurvati. 2005. Metabolic cardioprotection by pyruvate: recent progress. Experimental Biology and Medicine (Maywood, N.J.) 230: 435–443.CrossRefGoogle Scholar
  5. 5.
    Kristo, G., Y. Yoshimura, J. Niu, B.J. Keith, R.M. Mentzer Jr., R. Bünger, and R.D. Lasley. 2004. The intermediary metabolite pyruvate attenuates stunning and reduces infarct size in in vivo porcine myocardium. Am J Physiol Herat Circ Physiol 286: H517–H524.CrossRefGoogle Scholar
  6. 6.
    Yi, J.S., T.Y. Kim, D. Kyu Kim, and J.Y. Koh. 2007. Systemic pyruvate administration markedly reduces infarcts and motor deficits in rat models of transient and permanent focal cerebral ischemia. Neurobiology of Disease 26: 94–104.CrossRefGoogle Scholar
  7. 7.
    Wang, Q., M. van Hoecke, X.N. Tang, H. Lee, Z. Zheng, R.A. Swanson, and M.A. Yenari. 2009. Pyruvate protects against experimental stroke via an anti-inflammatory mechanism. Neurobiology of Disease 36: 223–231.CrossRefGoogle Scholar
  8. 8.
    Brencher, L., F. Petrat, K. Stych, et al. 2017. Effect of Glycine, Pyruvate, and Resveratrol on the Regeneration Process of Postischemic Intestinal Mucosa. BioMed Research International 2017: 1072969.CrossRefGoogle Scholar
  9. 9.
    Petrat, F., T. Rönn, and H. De Groot. 2011. Protection by pyruvate infusion in a rat model serve intestinal ischemia-reperfusion injury. The Journal of Surgical Research 167: e93–e101.CrossRefGoogle Scholar
  10. 10.
    Sileri, P., M. Brown, S. Morini, C. Rastellini, E. Benedetti, and L. Cicalese. 2001. Pyruvate prevents intestinal functional changes following ischemia-reperfusion injury. Transplantation Proceedings 33: 852.CrossRefGoogle Scholar
  11. 11.
    Mongan, P.D., J.L. Fontana, R. Chen, and R. Bünger. 1999. Intravenous pyruvate prolongs survival during hemorrhagic shock in swine. The American Journal of Physiology 277: H2253–H2263.Google Scholar
  12. 12.
    Koustova, E., P. Rhee, T. Hancock, H. Chen, R. Inocencio, A. Jaskille, W. Hanes, C.R. Valeri, and H.B. Alam. 2003. Ketone and pyruvate Ringer's solutions decrease pulmonary apoptosis in a rat model of severe hemorrhagic shock and resuscitation. Surgery 134: 267–274.CrossRefGoogle Scholar
  13. 13.
    Hu, S., X.D. Bai, X.Q. Liu, H.B. Wang, Y.X. Zhong, T. Fang, and F.Q. Zhou. 2013. Pyruvate Ringer’s solution corrects lactic acidosis and prolongs survival during hemorrhagic shock in rats. The Journal of Emergency Medicine 45: 885–893.CrossRefGoogle Scholar
  14. 14.
    Liu, R., S.M. Wang, X.Q. Liu, S.J. Guo, H.B. Wang, S. Hu, F.Q. Zhou, and Z.Y. Sheng. 2016. Pyruvate alleviates lipid peroxidation and multiple-organ dysfunction in rats with hemorrhagic shock. The American Journal of Emergency Medicine 34: 525–530.CrossRefGoogle Scholar
  15. 15.
    Sharma, P., M. Vyacheslav, C. Carissa, R. Vanessa, and M. Bodo. 2015. Pyruvate dose response studies targeting the vital signs following hemorrhagic shock. Journal of Emergencies Trauma and Shock 8: 159–166.CrossRefGoogle Scholar
  16. 16.
    Das, U.N. 2006. Pyruvate is an endogenous anti-inflammatory and anti-oxidant molecule. Medical Science Monitor 12: RA79–RA84.Google Scholar
  17. 17.
    Fink, M.P. 2008. Ethyl pyruvate. Current Opinion in Anaesthesiology 21: 160–167.CrossRefGoogle Scholar
  18. 18.
    Ulloa, L., M. Ochani, H. Yang, M. Tanovic, D. Halperin, R. Yang, C.J. Czura, M.P. Fink, and K.J. Tracey. 2002. Ethyl pyruvate prevents lethality in mice with established lethal sepsis and systemic inflammation. PNAS 99: 12351–12356.CrossRefGoogle Scholar
  19. 19.
    Kang, H., Z. Mao, Y. Zhao, T. Yin, Q. Song, L. Pan, X. Hu, J. Hu, and F. Zhou. 2016. Ethyl pyruvate protects against sepsis by regulating energy metabolism. Therapeutics and Clinical Risk Management 12: 287–294.Google Scholar
  20. 20.
    Jacobs, C.C., S.J. Holcombe, V.L. Cook, J.C. Gandy, J.G. Hauptman, and L.M. Sordillo. 2013. Ethyl pyruvate diminishes the inflammatory response to lipopolysaccharide infusion in horses. Equine Veterinary Journal 45: 333–339.CrossRefGoogle Scholar
  21. 21.
    Kung, C.W., Y.M. Lee, P.Y. Cheng, Y.J. Peng, and M.H. Yen. 2011. Ethyl pyruvate reduces acute lung injury via regulation of iNOS and HO-1 expression in endotoxemic rats. The Journal of Surgical Research 167: e323–e331.CrossRefGoogle Scholar
  22. 22.
    Hamburger, T., M. Broecker-Preuss, M. Hartmann, F.U. Schade, H. de Groot, and F. Petrat. 2013. Effects of glycine, pyruvate, resveratrol, and nitrite on tissue injury and cytokine response in endotoxemic rats. The Journal of Surgical Research 183: e7–e21.CrossRefGoogle Scholar
  23. 23.
    Brencher L, Oude Lansink M, and Effenberger-Neidnicht K. 2017. Administration of exogenous melatonin after the onset of systemic inflammation is hardly beneficial. Inflammation 40: 1672–1677.Google Scholar
  24. 24.
    Mallet, R.T., A.H. Olivencia-Yurvati, and R. Bunger. 2018. Pyruvate-enriched resuscitation for shock. Experimental Biology and Medicine (Maywood, N.J.) 243: 663–664.CrossRefGoogle Scholar
  25. 25.
    Kung, C.W., Y.M. Lee, and M.H. Yen. 2011. In vivo anticoagulant effect of ethyl pyruvate in endotoxemic rats. Thrombosis Research 127: 582–588.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute of Physiological ChemistryUniversity Hospital EssenEssenGermany
  2. 2.Clinic for Anesthesiology and Intensive CareUniversity Hospital EssenEssenGermany
  3. 3.Institute of PhysiologyUniversity Hospital EssenEssenGermany

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