Advertisement

Inflammation

, Volume 39, Issue 1, pp 447–456 | Cite as

Erythropoietin Pretreatment Attenuates Seawater Aspiration-Induced Acute Lung Injury in Rats

  • Mu-huo Ji
  • Jian-hua Tong
  • Yuan-hui Tan
  • Zhen-yu Cao
  • Cong-yang Ou
  • Wei-yan Li
  • Jian-jun Yang
  • Y. G. Peng
  • Si-hai ZhuEmail author
Original Article

ABSTRACT

Seawater drowning-induced acute lung injury (ALI) is a serious clinical condition characterized by increased alveolar-capillary permeability, excessive inflammatory responses, and refractory hypoxemia. However, current therapeutic options are largely supportive; thus, it is of great interest to search for alternative agents to treat seawater aspiration-induced ALI. Erythropoietin (EPO) is a multifunctional agent with antiinflammatory, antioxidative, and antiapoptotic properties. However, the effects of EPO on seawater aspiration-induced ALI remain unclear. In the present study, male rats were randomly assigned to the naive group, normal saline group, seawater group, or seawater + EPO group. EPO was administered intraperitoneally at 48 and 24 h before seawater aspiration. Arterial blood gas analysis was performed with a gas analyzer at baseline, 30 min, 1 h, 4 h, and 24 h after seawater aspiration, respectively. Histological scores, computed tomography scan, nuclear factor kappa B p65, inducible nitric oxide synthase, caspase-3, tumor necrosis factor-alpha, interleukin (IL)-1β, IL-6, IL-10, wet-to-dry weight ratio, myeloperoxidase activity, malondialdehyde, and superoxide dismutase in the lung were determined 30 min after seawater aspiration. Our results showed that EPO pretreatment alleviated seawater aspiration-induced ALI, as indicated by increased arterial partial oxygen tension and decreased lung histological scores. Furthermore, EPO pretreatment attenuated seawater aspiration-induced increase in the expressions of pulmonary nuclear factor kappa B p65, inducible nitric oxide synthase, caspase-3, tumor necrosis factor-alpha, IL-1β, myeloperoxidase activity, and malondialdehyde when compared with the seawater group. Collectively, our study suggested that EPO pretreatment attenuates seawater aspiration-induced ALI by down-regulation of pulmonary pro-inflammatory cytokines, oxidative stress, and apoptosis.

KEY WORDS

seawater acute lung injury erythropoietin cytokines reactive oxygen species 

Notes

ACKNOWLEDGMENTS

The study was supported by grants (YYZD2014001) from the Jinling hospital.

The authors have no potential conflicts of interest to disclose.

Compliance with Ethical Standard

This study was approved by the Ethics Committee of Jinling Hospital, Nanjing University and was performed in accordance with the Guide for the Care and Use of Laboratory Animals from the National Institutes of Health.

REFERENCES

  1. 1.
    Wallis, B.A., K. Watt, R.C. Franklin, J.W. Nixon, and R.M. Kimble. 2015. Drowning mortality and morbidity rates in children and adolescents 0-19 yrs: a population-based study in Queensland, Australia. PLoS One 10(2): e0117948. doi: 10.1371/journal.pone.0117948.PubMedCentralCrossRefPubMedGoogle Scholar
  2. 2.
    Marik, P.E. 2014. Iatrogenic salt water drowning and the hazards of a high central venous pressure. Annals of Intensive Care 4: 21. doi: 10.1186/s13613-014-0021-0.PubMedCentralCrossRefPubMedGoogle Scholar
  3. 3.
    Liu, Z., R. Xi, Z. Zhang, W. Li, Y. Liu, F. Jin, and X. Wang. 2014. 4-hydroxyphenylacetic acid attenuated inflammation and edema via suppressing HIF-1α in seawater aspiration-induced lung injury in rats. International Journal of Molecular Sciences 15(7): 12861–84. doi: 10.3390/ijms150712861.PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    Liu, Q.P., D.X. Zhou, L. Sun, L. Ling, C.G. Wu, P. Lin, and S.P. Han. 2014. Bone marrow mesenchymal stem cells ameliorates seawater-exposure-induced acute lung injury by inhibiting autophagy in lung tissue. Pathology Research International 2014: 104962. doi: 10.1155/2014/104962.PubMedCentralCrossRefPubMedGoogle Scholar
  5. 5.
    Zhang, M., M. Dong, W. Liu, L. Wang, Y. Luo, Z. Li, and F. Jin. 2014. 1α,25-dihydroxyvitamin D3 ameliorates seawater aspiration-induced acute lung injury via NF-κB and RhoA/Rho kinase pathways. PloS One 9(8): e104507. doi: 10.1371/journal.pone.0104507.PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Liu, W., M. Dong, L. Bo, C. Li, Q. Liu, Y. Li, L. Ma, Y. Xie, E. Fu, D. Mu, L. Pan, F. Jin, and Z. Li. 2014. Epigallocatechin-3-gallate ameliorates seawater aspiration-induced acute lung injury via regulating inflammatory cytokines and inhibiting JAK/STAT1 pathway in rats. Mediators of Inflammation 2014: 612593. doi: 10.1155/2014/612593.PubMedCentralPubMedGoogle Scholar
  7. 7.
    Debeljak, N., P. Solár, and A.J. Sytkowski. 2014. Erythropoietin and cancer: the unintended consequences of anemia correction. Frontiers in Immunology 5: 563. doi: 10.3389/fimmu.2014.00563.PubMedCentralCrossRefPubMedGoogle Scholar
  8. 8.
    Aoshiba, K., S. Onizawa, T. Tsuji, and A. Nagai. 2009. Therapeutic effects of erythropoietin in murine models of endotoxin shock. Critical Care Medicine 37(3): 889–98. doi: 10.1097/CCM.0b013e31819b8371.CrossRefPubMedGoogle Scholar
  9. 9.
    Köroğlu, T.F., O. Yılmaz, N. Gökmen, K. Tuğyan, H. Baskın, and M.Y. Eğrilmez. 2013. Erythropoietin prevents lymphoid apoptosis but has no effect on survival in experimental sepsis. Pediatric Research 74(2): 148–53. doi: 10.1038/pr.2013.86.CrossRefPubMedGoogle Scholar
  10. 10.
    Stoyanoff, T.R., J.S. Todaro, M.V. Aguirre, M.C. Zimmermann, and N.C. Brandan. 2014. Amelioration of lipopolysaccharide-induced acute kidney injury by erythropoietin: involvement of mitochondria-regulated apoptosis. Toxicology 318: 13–21. doi: 10.1016/j.tox.2014.01.011.CrossRefPubMedGoogle Scholar
  11. 11.
    Mitra, A., S. Bansal, W. Wang, S. Falk, E. Zolty, and R.W. Schrier. 2007. Erythropoietin ameliorates renal dysfunction during endotoxaemia. Nephrology, Dialysis, Transplantation 22(8): 2349–53.CrossRefPubMedGoogle Scholar
  12. 12.
    Rocha, J., M. Eduardo-Figueira, A. Barateiro, A. Fernandes, D. Brites, R. Pinto, M. Freitas, E. Fernandes, H. Mota-Filipe, and B. Sepodes. 2015. Erythropoietin reduces acute lung injury and multiple organ failure/dysfunction associated to a scald-burn inflammatory injury in the rat. Inflammation 38(1): 312–26. doi: 10.1007/s10753-014-0035-7.CrossRefPubMedGoogle Scholar
  13. 13.
    Ji, M., R. Li, G.M. Li, Y. Fan, L. Dong, J. Yang, Y.G. Peng, and J. Wu. 2012. Effects of combined levosimendan and vasopressin on pulmonary function in porcine septic shock. Inflammation 35(3): 871–80. doi: 10.1007/s10753-011-9388-3.CrossRefPubMedGoogle Scholar
  14. 14.
    Li, G.M., M.H. Ji, X.J. Sun, Q.T. Zeng, M. Tian, Y.X. Fan, W.Y. Li, N. Li, and J.J. Yang. 2013. Effects of hydrogen-rich saline treatment on polymicrobial sepsis. The Journal of Surgical Research 181(2): 279–86. doi: 10.1016/j.jss.2012.06.058.CrossRefPubMedGoogle Scholar
  15. 15.
    Ma, L., Y. Li, Y. Zhao, Q. Wang, Y. Nan, D. Mu, W. Li, R. Sun, F. Jin, and X. Liu. 2013. 3,5,4’-tri-O-acetylresveratrol ameliorates seawater exposure-induced lung injury by upregulating connexin 43 expression in lung. Mediators of Inflammation 2013: 182132. doi: 10.1155/2013/182132.PubMedCentralCrossRefPubMedGoogle Scholar
  16. 16.
    Zhao, W., X. Gan, G. Su, G. Wanling, S. Li, Z. Hei, C. Yang, and H. Wang. 2014. The interaction between oxidative stress and mast cell activation plays a role in acute lung injuries induced by intestinal ischemia-reperfusion. The Journal of Surgical Research 187(2): 542–52. doi: 10.1016/j.jss.2013.10.033.CrossRefPubMedGoogle Scholar
  17. 17.
    Wu, F., W.S. Szczepaniak, S. Shiva, H. Liu, Y. Wang, L. Wang, Y. Wang, E.E. Kelley, A.F. Chen, M.T. Gladwin, and B.J. McVerry. 2014. Nox2-dependent glutathionylation of endothelial NOS leads to uncoupled superoxide production and endothelial barrier dysfunction in acute lung injury. American Journal of Physiology. Lung Cellular and Molecular Physiology 307(12): L987–97. doi: 10.1152/ajplung.00063.2014.PubMedCentralCrossRefPubMedGoogle Scholar
  18. 18.
    Zhang, L., H. Wang, T. Wang, N. Jiang, P. Yu, Y. Chong, and F. Fu. 2015. Ferulic acid ameliorates nerve injury induced by cerebral ischemia in rats. Experimental and Therapeutic Medicine 9(3): 972–976.PubMedCentralPubMedGoogle Scholar
  19. 19.
    Miljus, N., S. Heibeck, M. Jarrar, M. Micke, D. Ostrowski, H. Ehrenreich, and R. Heinrich. 2014. Erythropoietin-mediated protection of insect brain neurons involves JAK and STAT but not PI3K transduction pathways. Neuroscience 258: 218–27. doi: 10.1016/j.neuroscience.2013.11.020.CrossRefPubMedGoogle Scholar
  20. 20.
    Napolitano, L.M., T.C. Fabian, K.M. Kelly, J.A. Bailey, E.F. Block, W. Langholff, C. Enny, and H.L. Corwin. 2008. Improved survival of critically ill trauma patients treated with recombinant human erythropoietin. The Journal of Trauma 65(2): 285–97. doi: 10.1097/TA.0b013e31817f2c6e.CrossRefPubMedGoogle Scholar
  21. 21.
    Borovnik-Lesjak, V., K. Whitehouse, A. Baetiong, B. Artin, J. Radhakrishnan, and R.J. Gazmuri. 2013. High-dose erythropoietin during cardiac resuscitation lessens postresuscitation myocardial stunning in swine. Translational Research 162(2): 110–21. doi: 10.1016/j.trsl.2013.06.002.CrossRefPubMedGoogle Scholar
  22. 22.
    Radhakrishnan, J., M.P. Upadhyaya, M. Ng, A. Edelheit, H.M. Moy, I.M. Ayoub, and R.J. Gazmuri. 2013. Erythropoietin facilitates resuscitation from ventricular fibrillation by signaling protection of mitochondrial bioenergetic function in rats. American Journal of Translational Research 5(3): 316–26.PubMedCentralPubMedGoogle Scholar
  23. 23.
    Incagnoli, P., A. Ramond, M. Joyeux-Faure, J.L. Pépin, P. Lévy, and C. Ribuot. 2009. Erythropoietin improved initial resuscitation and increased survival after cardiac arrest in rats. Resuscitation 80(6): 696–700. doi: 10.1016/j.resuscitation.2009.03.024.CrossRefPubMedGoogle Scholar
  24. 24.
    Vasileiou, P.V., T. Xanthos, D. Barouxis, C. Pantazopoulos, A.E. Papalois, P. Lelovas, O. Kotsilianou, P. Pliatsika, E. Kouskouni, and N. Iacovidou. 2014. Erythropoietin administration facilitates return of spontaneous circulation and improves survival in a pig model of cardiac arrest. The American Journal of Emergency Medicine 32(8): 871–7. doi: 10.1016/j.ajem.2014.04.036.CrossRefPubMedGoogle Scholar
  25. 25.
    Grmec, S., M. Strnad, D. Kupnik, A. Sinkovic, and R.J. Gazmuri. 2009. Erythropoietin facilitates the return of spontaneous circulation and survival in victims of out-of-hospital cardiac arrest. Resuscitation 80(6): 631–7. doi: 10.1016/j.resuscitation.2009.03.010.CrossRefPubMedGoogle Scholar
  26. 26.
    Polglase, G.R., S.K. Barton, J.M. Melville, V. Zahra, M.J. Wallace, M.L. Siew, M. Tolcos, and T.J. Moss. 2014. Prophylactic erythropoietin exacerbates ventilation-induced lung inflammation and injury in preterm lambs. The Journal of Physiology 592(Pt 9): 1993–2002. doi: 10.1113/jphysiol.2013.270348.PubMedCentralCrossRefPubMedGoogle Scholar
  27. 27.
    Rui, M., Y.Y. Duan, X.H. Zhang, H.L. Wang, and D.P. Wang. 2012. Urinary trypsin inhibitor attenuates seawater-induced acute lung injury by influencing the activities of nuclear factor-ĸB and its related inflammatory mediators. Respiration 83(4): 335–43. doi: 10.1159/000333378.CrossRefPubMedGoogle Scholar
  28. 28.
    He, G., C. Dong, Z. Luan, B.M. McAllan, T. Xu, L. Zhao, and J. Qiao. 2013. Oxygen free radical involvement in acute lung injury induced by H5N1 virus in mice. Influenza and Other Respiratory Viruses 7(6): 945–53. doi: 10.1111/irv.12067.PubMedCentralCrossRefPubMedGoogle Scholar
  29. 29.
    Tajima, S., M. Soda, M. Bando, M. Enomoto, H. Yamasawa, S. Ohno, T. Takada, E. Suzuki, F. Gejyo, and Y. Sugiyama. 2008. Preventive effects of edaravone, a free radical scavenger, on lipopolysaccharide-induced lung injury in mice. Respirology 13(5): 646–53. doi: 10.1111/j.1440-1843.2008.01322.x.CrossRefPubMedGoogle Scholar
  30. 30.
    Baboolal, H.A., F. Ichinose, R. Ullrich, N. Kawai, K.D. Bloch, and W.M. Zapol. 2002. Reactive oxygen species scavengers attenuate endotoxin-induced impairment of hypoxic pulmonary vasoconstriction in mice. Anesthesiology 97(5): 1227–33.CrossRefPubMedGoogle Scholar
  31. 31.
    Yamamoto, Y., L.E. Sousse, P. Enkhbaatar, E.R. Kraft, D.J. Deyo, C.L. Wright, A. Taylor, M.G. Traber, R.A. Cox, H.K. Hawkins, S.W. Rehberg, L.D. Traber, D.N. Herndon, and D.L. Traber. 2012. γ-tocopherol nebulization decreases oxidative stress, arginase activity, and collagen deposition after burn and smoke inhalation in the ovine model. Shock 38(6): 671–6. doi: 10.1097/SHK.0b013e3182758759.PubMedCentralPubMedGoogle Scholar
  32. 32.
    Liu, Q.S., Z.W. Cheng, J.G. Xiong, S. Cheng, X.F. He, and X.C. Li. 2015. Erythropoietin pretreatment exerts anti-inflammatory effects in hepatic ischemia/reperfusion-injured rats via suppression of the TLR2/NF-κB pathway. Transplantation Proceedings 47(2): 283–9. doi: 10.1016/j.transproceed.2014.10.045.CrossRefPubMedGoogle Scholar
  33. 33.
    Gobe, G.C., C. Morais, D.A. Vesey, and D.W. Johnson. 2013. Use of high-dose erythropoietin for repair after injury: a comparison of outcomes in heart and kidney. Journal Nephropathology 2(3): 154–65. doi:10.12860/JNP.2013.27.Google Scholar
  34. 34.
    Gross, C.M., R. Rafikov, S. Kumar, S. Aggarwal, P.B. Ham Iii, M.L. Meadows, M. Cherian-Shaw, A. Kangath, S. Sridhar, R. Lucas, and S.M. Black. 2015. Endothelial nitric oxide synthase deficient mice are protected from lipopolysaccharide induced acute lung injury. PloS One 10(3): e0119918. doi: 10.1371/journal.pone.0119918.PubMedCentralCrossRefPubMedGoogle Scholar
  35. 35.
    Han, F., Y. Luo, Y. Li, Z. Liu, D. Xu, F. Jin, and Z. Li. 2012. Seawater induces apoptosis in alveolar epithelial cells via the Fas/FasL-mediated pathway. Respiratory Physiology & Neurobiology 182(2-3): 71–80. doi: 10.1016/j.resp.2012.05.012.CrossRefGoogle Scholar
  36. 36.
    MacRedmond, R., G.K. Singhera, and D.R. Dorscheid. 2009. Erythropoietin inhibits respiratory epithelial cell apoptosis in a model of acute lung injury. The European Respiratory Journal 33(6): 1403–14. doi: 10.1183/09031936.00084608.CrossRefPubMedGoogle Scholar
  37. 37.
    Tascilar, O., G.K. Cakmak, I.O. Tekin, A.U. Emre, B.H. Ucan, B. Bahadir, S. Acikgoz, O. Irkorucu, K. Karakaya, H. Balbaloglu, G. Kertis, H. Ankarali, and M. Comert. 2007. Protective effects of erythropoietin against acute lung injury in a rat model of acute necrotizing pancreatitis. World Journal of Gastroenterology 13(46): 6172–82.PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Mu-huo Ji
    • 1
  • Jian-hua Tong
    • 1
  • Yuan-hui Tan
    • 1
  • Zhen-yu Cao
    • 2
  • Cong-yang Ou
    • 2
  • Wei-yan Li
    • 1
  • Jian-jun Yang
    • 1
  • Y. G. Peng
    • 3
  • Si-hai Zhu
    • 1
    Email author
  1. 1.Department of Anesthesiology, Jinling Hospital, School of MedicineNanjing UniversityNanjingChina
  2. 2.Department of Critical Care MedicineZhoushanChina
  3. 3.Department of AnesthesiologyUniversity of Florida College of MedicineGainesvilleUSA

Personalised recommendations