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Protective Effect of Recombinant Human Brain Natriuretic Peptide on Acute Renal Injury Induced by Endotoxin in Canines

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Abstract

The objective of this study was to evaluate the protective effect of recombinant human brain natriuretic peptide (rhBNP) on endotoxin-induced acute kidney injury (AKI) in canine model of septic shock and its potential mechanisms. Dogs with endotoxin-induced septic shock were subjected to intravenous infusion of saline solution or rhBNP at the concentrations of 5 μg/kg (low-dose intervention group) or 10 μg/kg (high-dose intervention group). At 0, 2, 4, 8, and 12 h, the systemic vascular resistance index (SVRI) as well as serum levels of high mobility group box 1 protein (HMGB-1) and creatinine were measured, and kidney tissue samples were taken for histological examination. We have found that low and high doses of rhBNP could significantly reduce kidney tissue damage, such as tubular epithelial swelling and atrophy, and interstitial cell swelling in response to LPS injection in the dog sepsis models. rhBNP administration significantly reduced SVRI and serum levels of creatinine in dogs with LPS-induced sepsis in a dose-dependent manner, and attenuated the rise in the circulating HMGB-1. In conclusion, these findings suggest that rhBNP may exert dose-dependent protective effect on kidney tissue with endotoxin-induced injury, and this effect may be associated with the changes in blood levels of HMGB-1. rhBNP may be considered as therapeutic agents for treating sepsis-induced AKI.

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References

  1. Dombrovskiy, V. Y., Martin, A. A., Sunderram, J., & Paz, H. L. (2007). Rapid increase in hospitalization and mortality rates for severe sepsis in the United States: a trend analysis from 1993 to 2003. Critical Care Medicine, 35, 1244–1250.

    Article  PubMed  Google Scholar 

  2. Koçkara, A., & Kayataş, M. (2013). Renal cell apoptosis and new treatment options in sepsis-induced acute kidney injury. Renal Failure, 35, 291–294.

    Article  PubMed  Google Scholar 

  3. Peng, T., Shen, E., Fan, J., Zhang, Y., Arnold, J. M., & Feng, Q. (2008). Disruption of phospholipase C gamma1 signalling attenuates cardiac tumor necrosis factor-alpha expression and improves myocardial function during endotoxemia. Cardiovascular Research, 78, 90–97.

    Article  PubMed  CAS  Google Scholar 

  4. Yang, H., Song, Z., Jin, H., Cui, Y., Hou, M., & Gao, Y. (2014). Protective effect of rhBNP on intestinal injury in the canine models of sepsis. International Immunopharmacology, 19, 262–266.

    Article  PubMed  CAS  Google Scholar 

  5. Song, Z., Cui, Y., Ding, M. Z., Jin, H. X., & Gao, Y. (2013). Protective effects of recombinant human brain natriuretic peptide against LPS-Induced acute lung injury in dogs. International Immunopharmacology, 17, 508–512.

    Article  PubMed  CAS  Google Scholar 

  6. Cheng, B., Xie, G., Yao, S., Wu, X., Guo, Q., Gu, M., et al. (2007). Epidemiology of severe sepsis in critically ill surgical patients in ten university hospitals in China. Critical Care Medicine, 35, 2538–2546.

    Article  PubMed  Google Scholar 

  7. Kumaraswamy, S. B., Linder, A., Åkesson, P., & Dahlbäck, B. (2011). Decreased Plasma Concentrations of Apolipoprotein M in Sepsis and Systemic Inflammatory Response Syndromes. Critical Care, 16, 60–62.

    Article  Google Scholar 

  8. Russell, J. A. (2006). Management of sepsis. The New England Journal of Medicine, 355, 1699–1713.

    Article  PubMed  CAS  Google Scholar 

  9. Rangel-Frausto, M. S., Pittet, D., Costigan, M., et al. (1995). The natural history of the systemic inflammatory response syndrome (SIRS): A prospective study. The Journal of the American Medical Association, 273, 117–123.

    Article  CAS  Google Scholar 

  10. Aksoy, Y., Yapanoglu, T., Aksou, H., & Yildirim, A. K. (2004). The effect of dehydroepiandrosterone on renal ischemia-reperfusion-induced oxidative stress in rabbits. Urological Research, 32, 93–96.

    Article  PubMed  CAS  Google Scholar 

  11. Van Amersfoort, E. S., Van Berkel, T. J. C., & Kuiper, J. (2003). Receptors, mediators, and mechanisms involved in bacterial sepsis and septic shock. Clinical Microbiology Reviews, 16(3), 379–414.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Doi, K., Leelahavanichkul, A., Yuen, P. S. T., & Star, R. A. J. (2009). Animal models of sepsis and sepsis-induced kidney injury. Journal of Clinical Investigation, 119(10), 2868–2878.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  13. Bone, R. C. (1991). Gram-negative sepsis. Background, clinical features, and intervention. Chest, 100, 802–808.

    Article  PubMed  CAS  Google Scholar 

  14. Yuong, J. D. (2004). The heart and circulation in severe sepsis. British Journal of Anaesthesia, 93, 114–120.

    Article  Google Scholar 

  15. Maekawa, K., Sudoh, T., Furusawa, M., Minamino, N., Kangawa, K., Ohkubo, H., et al. (1988). Cloning and sequence analysis of cDNA encoding a precursor for porcine brain natriuretic peptide. Biochemical and Biophysical Research Communications, 157, 410–416.

    Article  PubMed  CAS  Google Scholar 

  16. Li, N., Zhang, Y., Fan, S., Xing, J., & Liu, H. (2013). BNP and NT-proBNP levels in patients with sepsis. Frontiers in Bioscience, 18, 1237–1243.

    Article  CAS  Google Scholar 

  17. Wang, F., Wu, Y., Tang, L., Zhu, W., Chen, F., Xu, T., et al. (2012). Brain natriuretic peptide for prediction of mortality in patients with sepsis: a systematic review and meta-analysis. Critical Care, 16, R74.

    Article  PubMed  PubMed Central  Google Scholar 

  18. McLean, A. S., Huang, S. J., Hyams, S., Poh, G., Nalos, M., Pandit, R., et al. (2007). Prognostic values of B-type natriuretic peptide in severe sepsis and septic shock. Critical Care Medicine, 35, 1019–1026.

    Article  PubMed  CAS  Google Scholar 

  19. Potter, L. R., et al. (2009). Natriuretic peptides: their structures, receptors, physiologic functions and therapeutic applications. Handbook of Experimental Pharmacology, 191, 341–366.

    Article  PubMed  CAS  Google Scholar 

  20. Wang, W., Zolty, E., Falk, S., Summer, S., Stearman, R., Geraci, M., et al. (2007). Prostacyclin in endotoxemia-induced acute kidney injury: cyclooxygenase inhibition and renal prostacyclin synthase transgenic mice. American Journal of Physiology Renal Physiology, 293, F1131–F1136.

    Article  PubMed  CAS  Google Scholar 

  21. Chertow, G. M., Burdick, E., Honour, M., Bonventre, J. V., & Bates, D. W. (1999). Acute kidney injury, mortality, length of stay, and mice. Science, 285, 248–251.

    Article  Google Scholar 

  22. Li, W., Li, J., Ashok, M., Wu, R., Chen, D., Yang, L., et al. (2000). Tracey KJ, Wang P, Sama AE, Wang H High mobility group 1 protein (HMG-1) stimulates proinflammatory cy-tokine synthesis in human monocytes. Journal of Experimental Medicine, 192, 565–570.

    Article  Google Scholar 

  23. Ulloa, L., Brunner, M., Ramos, L., & Deitch, E. A. (2009). Selentific and clinical challenges in sepsis. Current Pharmaceutical Design, 15, 1918–1935.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  24. Hou, L. C., Qin, M. Z., Zheng, L. N., Lu, Y., Wang, Q., Peng, D. R., et al. (2009). Severity of sepsis is correlated with the elevation of serum high-mobility group box 1 in rats. Chinese Medical Journal, 122, 449–454.

    PubMed  CAS  Google Scholar 

  25. Mori, M., Yamanashi, Y., Kobayashi, K., & Sakamoto, A. (2010). Atrial natriuretic peptide alleviates cardiovascular and metabolic disorders in a rat endotoxemia model: A possible role for its anti-inflammatory properties. Journal of Nippon Medical School, 77, 296–305.

    Article  PubMed  CAS  Google Scholar 

  26. Schmetterer, L., & Polak, K. (2001). Role of nitric oxide in the control of ocular blood. Progress in Retinal and Eye Research, 20, 823–847.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Yan Gao.

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Li, N., Jin, HX., Song, Z. et al. Protective Effect of Recombinant Human Brain Natriuretic Peptide on Acute Renal Injury Induced by Endotoxin in Canines. Cell Biochem Biophys 70, 1317–1324 (2014). https://doi.org/10.1007/s12013-014-0057-7

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