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Preventive Effects of Valnemulin on Lipopolysaccharide-Induced Acute Lung Injury in Mice

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Abstract

Valnemulin reportedly regulates inflammatory responses in addition to its in vitro antibacterial activity. In this study, we established a mouse model of lipopolysaccharide (LPS)-induced inflammatory lung injury and investigated the effect of valnemulin (100 mg/kg) on acute lung injury (ALI) 8 h after LPS challenge. We prepared bronchoalveolar lavage fluid (BALF) for measuring protein concentrations, cytokine levels, and superoxidase dismutase (SOD) activity, and collected lungs for assaying wet-to-dry weight (W/D) ratios, myeloperoxidase (MPO) activity, cytokine mRNA expression, and histological change. We found that the pre-administration of valnemulin significantly decreases the W/D ratio of lungs, protein concentrations, and the number of total cells, neutrophils, macrophages, and leukomonocytes, and histologic analysis indicates that valnemulin significantly attenuates tissue injury. Furthermore, valnemulin significantly increases LPS-induced SOD activity in BALF and decreases lung MPO activity as well. In addition, valnemulin also inhibits the production of tumor necrosis factor-α, interleukin-6, and interleukin-1β, which is consistent with mRNA expression in lung. The results showed that valnemulin had a protective effect on LPS-induced ALI in mice.

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References

  1. Fujishima, S., and N. Aikawa. 1995. Neutrophil-mediated tissue injury and its modulation. Intensive Care Medicine 21: 277–285.

    Article  CAS  PubMed  Google Scholar 

  2. Ware, L.B., and M.A. Matthay. 2000. The acute respiratory distress syndrome. New England Journal of Medicine 342: 1334–1349.

    Article  CAS  PubMed  Google Scholar 

  3. Bosma, K., V. Fanelli, and V.M. Ranieri. 2005. Acute respiratory distress syndrome: update on the latest developments in basic and clinical research. Current Opinion in Anaesthesiology 18: 137–145.

    Article  PubMed  Google Scholar 

  4. Lee, W.L., and G.P. Downey. 2001. Neutrophil activation and acute lung injury. Current Opinion in Critical Care 7: 1–7.

    Article  CAS  PubMed  Google Scholar 

  5. Bhatia, M., and S. Moochhala. 2004. Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome. Journal of Pathology 202: 145–156.

    Article  CAS  PubMed  Google Scholar 

  6. Riedemann, N.C., R.F. Guo, and P.A. Ward. 2003. The enigma of sepsis. Journal of Clinical Investigation 112: 460–467.

    CAS  PubMed  Google Scholar 

  7. Strieter, R.M., S.L. Kunkel, M.P. Keane, and T.J. Standiford. 1999. Chemokines in lung injury: Thomas A Neff Lecture. Chest 116: 103S–110S.

    Article  CAS  PubMed  Google Scholar 

  8. Kitamura, Y., S. Hashimoto, N. Mizuta, A. Kobayashi, K. Kooguchi, I. Fujiwara, and H. Nakajima. 2001. Fas/Fasl-dependent apoptosis of alveolar cells after lipopolysaccharide-induced lung injury in mice. American Journal of Respiratory and Critical Care Medicine 163: 762–769.

    CAS  PubMed  Google Scholar 

  9. Wu, Y., M. Singer, F. Thouron, M. Alaoui-El-Azher, and L. Touqui. 2002. Effect of surfactant on pulmonary expression of type IIA PLA(2) in an animal model of acute lung injury. American Journal of Physiology. Lung Cellular and Molecular Physiology 282: L743–L750.

    CAS  PubMed  Google Scholar 

  10. Koller, K., and F. Schwarz. 2001. Formulation of valnemulin [P]. US:6284792.

  11. Windsor, H.M., P.H. Ripley, P.C.T. Hannan 1996. An in vitro investigation of the sensitivity of German field isolates of M. hyopneumoniae and M. hyosynoviae to SDZ PMD 296, a new pleuromulin derivate. In: Proceedings of the 14th IPVS Congress, 226. Bologna, Italy.

  12. Hannan, P.C., H.M. Windsor, and P.H. Ripley. 1997. in vitro susceptibilities of recent field isolates of Mycoplasma hyopneumoniae and Mycoplasma hyosynoviae to valnemulin (Econor), tiamulin and enrofloxacin and the in vitro development of resistance to certain antimicrobial agents in Mycoplasma hyopneumoniae. Research in Veterinary Science 63: 157–160.

    Article  CAS  PubMed  Google Scholar 

  13. Long, K.S., L.H. Hansen, L. Jakobsen, and B. Vester. 2006. Interaction of pleuromutilin derivatives with the ribosomal peptidyl transferase center. Antimicrobial Agents and Chemotherapy 50: 1458–1462.

    Article  CAS  PubMed  Google Scholar 

  14. Heilmann, C., L. Jensen, J.S. Jensen, K. Lundstrom, D. Windsor, H. Windsor, and D. Webster. 2001. Treatment of resistant Mycoplasma infection in immunocompromised patients with a new pleuromutilin antibiotic. Journal of Infection 43: 234–238.

    Article  CAS  PubMed  Google Scholar 

  15. Zhang, X., H. Li, H. Feng, H. Xiong, L. Zhang, Y. Song, L. Yu, and X. Deng. 2009. Valnemulin downregulates nitric oxide, prostaglandin E2, and cytokine production via inhibition of NF–kappaB and MAPK activity. International Immunopharmacology 9: 810–816.

    Article  CAS  PubMed  Google Scholar 

  16. Ysebaert, D.K., G.K.E. De, S.R. Vercauteren, M. Ghielli, G.A. Verpooten, E.J. Eyskens, and B.M.E. De. 2000. Identification and kinetics of leukocytes after severe ischaemia/reperfusion renal injury. Nephrology, Dialysis, Transplantation 15: 1562–1574.

    Article  CAS  PubMed  Google Scholar 

  17. Mongan, L.C., T. Jones, and G. Patrick. 2000. Cytokine and free radical responses of alveolar macrophages in vitro to asbestos fibres. Cytokine 12: 1243–1247.

    Article  CAS  PubMed  Google Scholar 

  18. Shimazu, R., S. Akashi, H. Ogata, Y. Nagai, K. Fukudome, K. Miyake, and M. Kimoto. 1999. MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. Journal of Experimental Medicine 189: 1777–1782.

    Article  CAS  PubMed  Google Scholar 

  19. Szarka, R.J., N. Wang, L. Gordon, P.N. Nation, and R.H. Smith. 1997. A murine model of pulmonary damage induced by lipopolysaccharide via intranasal instillation. Journal of Immunological Methods 202: 49–57.

    Article  CAS  PubMed  Google Scholar 

  20. von Bismarck, P., K. Klemm, W.C.F. García, S. Winoto-Morbach, S. Schütze, and M.F. Krause. 2009. Selective NF–kappaB inhibition, but not dexamethasone, decreases acute lung injury in a newborn piglet airway inflammation model. Pulmonary Pharmacology and Therapeutics 22: 297–304.

    Article  Google Scholar 

  21. Lucas, R., A.D. Verin, S.M. Black, and J.D. Catravas. 2009. Regulators of endothelial and epithelial barrier integrity and function in acute lung injury. Biochemical Pharmacology 77: 1763–1772.

    Article  CAS  PubMed  Google Scholar 

  22. Staub Sr., N.C., K.E. Longworth, V. Serikov, E.H. Jerome, and T. Elsasser. 2001. Detergent inhibits 70–90% of responses to intravenous endotoxin in awake sheep. Journal of Applied Physiology 90: 1788–1797.

    Article  CAS  PubMed  Google Scholar 

  23. Sone, Y., V.B. Serikov, and N.C. Staub Sr. 1999. Intravascular macrophage depletion attenuates endotoxin lung injury in anesthetized sheep. Journal of Applied Physiology 87: 1354–1359.

    CAS  PubMed  Google Scholar 

  24. Mecklenburgh, K., J. Murray, T. Brazil, C. Ward, A.G. Rossi, and E.R. Chilvers. 1999. Role of neutrophil apoptosis in the resolution of pulmonary inflammation. Monaldi Archives for Chest Disease 54: 345–349.

    CAS  PubMed  Google Scholar 

  25. Cavaillon, J.M., and M. Adib-Conquy. 2005. Monocytes/macrophages and sepsis. Critical Care Medicine 33: S506–S509.

    Article  PubMed  Google Scholar 

  26. Klebanoff, S.J. 2005. Myeloperoxidase: Friend and foe. Journal of Leukocyte Biology 77: 598–625.

    Article  CAS  PubMed  Google Scholar 

  27. Winterbourn, C.C., M.C. Vissers, and A.J. Kettle. 2000. Myeloperoxidase. Current Opinion in Hematology 7: 53–58.

    Article  CAS  PubMed  Google Scholar 

  28. Roth, E., N. Manhart, and B. Wessner. 2004. Assessing the antioxidative status in critically ill patients. Current Opinion in Clinical Nutrition and Metabolic Care 7: 161–168.

    Article  CAS  PubMed  Google Scholar 

  29. Ueda, J., M.E. Starr, H. Takahashi, J. Du, L.Y. Chang, J.D. Crapo, B.M. Evers, and H. Saito. 2008. Decreased pulmonary extracellular superoxide dismutase during systemic inflammation. Free Radical Biology and Medicine 45: 897–904.

    Article  CAS  PubMed  Google Scholar 

  30. Kinnula, V.L., and J.D. Crapo. 2003. Superoxide dismutases in the lung and human lung diseases. American Journal of Respiratory and Critical Care Medicine 167: 1600–1619.

    Article  PubMed  Google Scholar 

  31. Bhattacharyya, J., S. Biswas, and A.G. Datta. 2004. Mode of action of endotoxin: role of free radicals and antioxidants. Current Medicinal Chemistry 11: 359–368.

    Article  CAS  PubMed  Google Scholar 

  32. Fattman, C.L., L.M. Schaefer, and T.D. Oury. 2003. Extracellular superoxide dismutase in biology and medicine. Free Radical Biology and Medicine 35: 236–256.

    Article  CAS  PubMed  Google Scholar 

  33. Macdonald, J., H.F. Galley, and N.R. Webster. 2003. Oxidative stress and gene expression in sepsis. British Journal of Anaesthesia 90: 221–232.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by a grant from the National Natural Science Foundation of China (No. 30671586).

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Authors and Affiliations

  1. Department of Veterinary Pharmacology, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, Jilin, 130062, People’s Republic of China

    Zhibao Chen, Xiao Chu, Xiaozhe Zhang, Lu Yu & Xuming Deng

  2. College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang, 163319, People’s Republic of China

    Zhibao Chen, Keji Song & Youshuai Jiang

  3. Department of Animal Medicine, Agricultural College of Yanbian University, Longjing, Jilin, 133400, People’s Republic of China

    Xuemei Zhang

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  1. Zhibao Chen
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  2. Xuemei Zhang
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  3. Xiao Chu
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  4. Xiaozhe Zhang
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  5. Keji Song
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  7. Lu Yu
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  8. Xuming Deng
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Correspondence to Lu Yu or Xuming Deng.

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Zhibao Chen and Xuemei Zhang contributed equally to this work.

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Chen, Z., Zhang, X., Chu, X. et al. Preventive Effects of Valnemulin on Lipopolysaccharide-Induced Acute Lung Injury in Mice. Inflammation 33, 306–314 (2010). https://doi.org/10.1007/s10753-010-9186-3

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  • DOI: https://doi.org/10.1007/s10753-010-9186-3

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