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Systemic perfluorohexane attenuates lung injury induced by lipopolysaccharide in rats: the role of heme oxygenase-1

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Abstract

Clinical trials with partial liquid ventilation demonstrate improvement in oxygenation, as well as some adverse side effects linked to the application of liquid perfluorocarbons (PFCs) during liquid ventilation. Thus, we examined the effects of systemic administration of PFC on acute lung injury (ALI) induced by lipopolysaccharide (LPS) and its effects on heme oxygenase-1 (HO-1), a compound that provides potent cytoprotection against lung injury.

Rats were assigned to one of six groups (n = 8). Thirty minutes after they were challenged with LPS aerosol inhalation, perfluorohexane was given intraperitoneally every two hours. Ten hours after LPS inhalation, bronchoalveolar lavage fluid (BALF) and lung tissue were obtained for enzyme linked immunosorbent assay, histologic, and Western-blot analyses. The results showed that perfluorohexane significantly decreased the wet to dry weight ratio, malondialdehyde (MDA) production, and myeloperoxidase (MPO) activity in the lung tissue. Also, perfluorohexane reduced the total protein content and levels of tumor necrosis factor-α (TNF-α) but increased the levels of the anti-inflammatory cytokine interleukin-10 (IL-10) in the BALF, resulting in decreased pulmonary edema and the infiltration of neutrophils into the lung tissues of LPS-treated rats. Furthermore, perfluorohexane increased HO-1 protein production and stimulated HO-1 activity in the lung tissue. Pre-treatment with Zinc protoporphyrin IX, an inhibitor of HO-1, decreased the protective effects of perfluorohexane in rats.

In summary, systemic perfluorohexane alleviates LPS-induced lung injury in rats, and HO-1 may be involved in the mechanism of this reduction.

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References

  1. Abraham E: Neutrophils and acute lung injury. Crit Care Med, 2003, 31, S195–199.

    Article  Google Scholar 

  2. Chang H, Kuo FC, Lai YS, Chou TC: Inhibition of inflammatory responses by FC-77, a perfluorochemical, in lipopolysaccharide-treated RAW 264.7 macrophages. Intensive Care Med, 2005, 31, 977–984.

    Article  Google Scholar 

  3. Chodorowski Z, Sein Anand J, Rybakowska I, Kaletha K: Heme oxygenase as a potential therapeutic target for hepatoprotection. Przegl Lek, 2007, 64, 360–362.

    PubMed  Google Scholar 

  4. Cox PN, Frndova H, Tan PS, Nakamura T, Miyasaka K, Sakurai Y, Middleton W et al.: Concealed air leak associated with large tidal volumes in partial liquid ventilation. Am J Respir Crit Care Med, 1997, 156, 992–997.

    Article  CAS  Google Scholar 

  5. Fernandez R, Sarma V, Younkin E, Hirschl RB, Ward PA, Younger JG: Exposure to perflubron is associated with decreased Syk phosphorylation in human neutro-phils. J Appl Physiol, 2001, 91, 1941–1947.

    Article  CAS  Google Scholar 

  6. Ferrándiz ML, Devesa I: Inducers of heme oxygenase-1. Curr Pharm Des, 2008, 14, 473–486.

    Article  Google Scholar 

  7. Fialkow L, Wang Y, Downey GP: Reactive oxygen and nitrogen species as signaling molecules regulating neutro-phil function. Free Radic Biol Med, 2007, 42, 153–164.

    Article  CAS  Google Scholar 

  8. Gorąca A, Józefowicz-Okonkwo G: Protective effects of early treatment with lipoic acid in LPS-induced lung injury in rats. J Physiol Pharmacol, 2007, 58, 541–549.

    PubMed  Google Scholar 

  9. Hirschl RB, Pranikoff T, Wise C, Overbeck MC, Gauger P, Schreiner RJ, Dechert R, Bartlett RH: Initial experience with partial liquid ventilation in adult patients with the acute respiratory distress syndrome. JAMA, 1996, 275, 383–389.

    Article  CAS  Google Scholar 

  10. Jiang L, Wang Q, Liu Y, Du M, Shen X, Guo X, Wu S: Total liquid ventilation reduces lung injury in piglets after cardiopulmonary bypass. Ann Thorac Surg, 2006, 82, 124–130.

    Article  Google Scholar 

  11. ** SW, Zhang L, Lian QQ, Liu D, Wu P, Yao SL, Ye DY: Posttreatment with aspirin-triggered lipoxin A4 analog attenuates lipopolysaccharide-induced acute lung injury in rats: the role of heme oxygenase-1. Anesth Analg, 2007, 104, 369–377.

    Article  CAS  Google Scholar 

  12. Kemming GI, Flondor M, Hanser A, Pallivathukal S, Holtmannspötter M, Kneisel FF, Reuter DA et al.: Effects of perfluorohexan vapor on gas exchange, respiratory mechanics, and lung histology in pigs with lung injury after endotoxin infusion. Anesthesiology, 2005, 103, 585–594.

    Article  Google Scholar 

  13. Kurutas EB, Cetinkaya A, Bulbuloglu E, Kantarceken B: Effects of antioxidant therapy on leukocyte myeloperoxi-dase and Cu/Zn-superoxide dismutase and plasma ma-londialdehyde levels in experimental colitis. Mediators Inflamm, 2005, 6, 390–394.

    Article  Google Scholar 

  14. Nader ND, Knight PR, Davidson BA, Safaee SS, Steinhorn DM: Systemic perfluorocarbons suppress the acute lung inflammation after gastric acid aspiration in rats. Anesth Analg, 2000, 90, 356–361.

    CAS  PubMed  Google Scholar 

  15. Ndisang JF, Wang R, Vannacci A, Marzocca C, Fantap-piè O, Mazzanti R, Mannaioni PF, Masini E: Haeme oxygenase-1 and cardiac anaphylaxis. Br J Pharmacol, 2001, 134, 1689–1696.

    Article  CAS  Google Scholar 

  16. Olszanecki R, Gebska A, Korbut R: The role of haem oxygenase-1 in the decrease of endothelial intercellular adhesion molecule-1 expression by curcumin. Basic Clin Pharmacol Toxicol, 2007, 101, 411–415.

    Article  CAS  Google Scholar 

  17. Otterbein LE, Choi AM: Heme oxygenase: colors of defense against cellular stress. Am J Physiol Lung Cell Mol Physiol, 2000, 279, L1029–1037.

    Article  CAS  Google Scholar 

  18. Reutershan J, Chang D, Hayes JK, Ley K: Protective effects of isoflurane pretreatment in endotoxin-induced lung injury. Anesthesiology, 2006, 104, 511–517.

    Article  CAS  Google Scholar 

  19. Ryter SW, Choi AM: Heme oxygenase-1: redox regulation of a stress protein in lung and cell culture models. Antioxid Redox Signal, 2005, 7, 80–91.

    Article  CAS  Google Scholar 

  20. Schoof E, von der Hardt K, Kandler MA, Abendroth F, Papadopoulos T, Rascher W, Dötsch J: Aerosolized per-fluorocarbon reduces adhesion molecule gene expression and neutrophil sequestration in acute respiratory distress. Eur J Pharmacol, 2002, 457, 195–200.

    Article  CAS  Google Scholar 

  21. Toews GB: Cytokines and the lung. Eur Respir J, Suppl. 2001, 34, 3s–17s.

    Article  CAS  Google Scholar 

  22. Zmijewski JW, Lorne E, Zhao X, Tsuruta Y, Sha Y, Liu G, Abraham E: Antiinflammatory effects of hydrogen peroxide in neutrophil activation and acute lung injury. Am J Respir Crit Care Med, 2009, 179, 694–704.

    Article  CAS  Google Scholar 

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Correspondence to Yong-Fei Tan.

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Ge, ZJ., Jiang, GJ., Zhao, YP. et al. Systemic perfluorohexane attenuates lung injury induced by lipopolysaccharide in rats: the role of heme oxygenase-1. Pharmacol. Rep 62, 170–177 (2010). https://doi.org/10.1016/S1734-1140(10)70254-1

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  • DOI: https://doi.org/10.1016/S1734-1140(10)70254-1

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