1887

Abstract

Oxidative stress injury is an important pathogenesis of influenza virus in critically ill patients. The present study investigated the efficacy of carnosine, an antioxidant and free radical scavenger, on a model of acute lung injury (ALI) induced by H9N2 swine influenza virus. Female specific-pathogen-free BALB/c mice were randomized into four groups and treated as follows: (1) H9N2 group, (2) mock control group, (3) H9N2+carnosine group and (4) carnosine control group. The H9N2 group mice were inoculated intranasally with A/Swine/Hebei/012/2008/ (H9N2) virus (100 μl) in allantoic fluid (AF), whilst mock-infected animals were intranasally inoculated with non-infectious AF. Carnosine [10 mg (kg body mass)] was administered orally (100 μl) for 7 days consecutively. The survival rate, lung water content, TNF-α and IL-1β levels, lung histopathology, myeloperoxidase (MPO) activity, and Toll-like receptor (TLR)-4 levels were determined at 2, 4, 6, 8 and 14 days after inoculation. Carnosine treatment effectively decreased the mortality (43 versus 75 %,  < 0.05), significantly ameliorated pathological lesions in lungs and decreased the lung wet/dry mass ratio ( < 0.05). It also inhibited MPO activity, suppressed TNF-α and IL-1β release, decreased the H9N2 viral titre, and markedly inhibited levels of TLR-4 mRNA and protein in the lungs of infected mice ( < 0.05), which supported the use of carnosine for managing severe influenza cases.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.000238
2015-10-01
2024-04-23
Loading full text...

Full text loading...

/deliver/fulltext/jgv/96/10/2939.html?itemId=/content/journal/jgv/10.1099/jgv.0.000238&mimeType=html&fmt=ahah

References

  1. Akaike T., Noguchi Y., Ijiri S., Setoguchi K., Suga M., Zheng Y.M., Dietzschold B., Maeda H. 1996; Pathogenesis of influenza virus-induced pneumonia: involvement of both nitric oxide and oxygen radicals. Proc Natl Acad Sci U S A 93:2448–2453 [View Article][PubMed]
    [Google Scholar]
  2. Amatore D., Sgarbanti R., Aquilano K., Baldelli S., Limongi D., Civitelli L., Nencioni L., Garaci E., Ciriolo M.R., Palamara A.T. 2015; Influenza virus replication in lung epithelial cells depends on redox-sensitive pathways activated by NOX4-derived ROS. Cell Microbiol 17:131–145 [View Article][PubMed]
    [Google Scholar]
  3. Babizhayev M.A., Deyev A.I. 2012; Management of the virulent influenza virus infection by oral formulation of nonhydrolyzed carnosine and isopeptide of carnosine attenuating proinflammatory cytokine-induced nitric oxide production. Am J Ther 19:e25–e47 [View Article][PubMed]
    [Google Scholar]
  4. Babizhayev M.A., Seguin M.C., Gueyne J., Evstigneeva R.P., Ageyeva E.A., Zheltukhina G.A. 1994; l-Carnosine (beta-alanyl-l-histidine) and carcinine (beta-alanylhistamine) act as natural antioxidants with hydroxyl-radical-scavenging and lipid-peroxidase activities. Biochem J 304:509–516[PubMed] [CrossRef]
    [Google Scholar]
  5. Babizhayev M.A., Deyev A.I., Yegorov Y.E.l-C. 2014; l-Carnosine modulates respiratory burst and reactive oxygen species production in neutrophil biochemistry and function: may oral dosage form of non-hydrolyzed dipeptide l-carnosine complement anti-infective anti-influenza flu treatment, prevention and self-care as an alternative to the conventional vaccination?. Curr Clin Pharmacol 9:93–115 [View Article][PubMed]
    [Google Scholar]
  6. Cai J., Chen Y., Seth S., Furukawa S., Compans R.W., Jones D.P. 2003; Inhibition of influenza infection by glutathione. Free Radic Biol Med 34:928–936 [View Article][PubMed]
    [Google Scholar]
  7. CDC 1997; Isolation of avian influenza A(H5N1) of viruses from humans: Hong Kong May–December 1997. MMWR Morb Mortal Wkly Rep 46:1204–1207[PubMed]
    [Google Scholar]
  8. Chan W.K.M., Decker E.A., Lee J.B., Butterfield D. 1994; EPR spin-trapping studies of the hydroxy radical scavenging activity of carnosine and related dipeptides. J Agric Food Chem 42:1407–1410 [View Article]
    [Google Scholar]
  9. Choi Y.H., Jin G.Y., Li L.C., Yan G.H. 2013; Inhibition of protein kinase C delta attenuates allergic airway inflammation through suppression of PI3K/Akt/mTOR/HIF-1 alpha/VEGF pathway. PLoS One 8:e81773 [View Article][PubMed]
    [Google Scholar]
  10. Chow C.W., Herrera Abreu M.T., Suzuki T., Downey G.P. 2003; Oxidative stress and acute lung injury. Am J Respir Cell Mol Biol 29:427–431 [View Article][PubMed]
    [Google Scholar]
  11. Cuzzocrea S., Genovese T., Failla M., Vecchio G., Fruciano M., Mazzon E., Di Paola R., Muià C., La Rosa C., other authors. 2007; Protective effect of orally administered carnosine on bleomycin-induced lung injury. Am J Physiol Lung Cell Mol Physiol 292:L1095–L1104 [View Article][PubMed]
    [Google Scholar]
  12. Dahl T.A., Midden W.R., Hartman P.E. 1988; Some prevalent biomolecules as defenses against singlet oxygen damage. Photochem Photobiol 47:357–362 [View Article][PubMed]
    [Google Scholar]
  13. Dong W., Li-Feng X., Cun-Lian W., Ming-Ju X., Rui-Hua Z., Ying L., Tong X. 2012; A mouse model of swine influenza virus H9N2 infection with acute lung injury. Acta Virol 56:227–233 [View Article][PubMed]
    [Google Scholar]
  14. Estenssoro E., Ríos F.G., Apezteguía C., Reina R., Neira J., Ceraso D.H., Orlandi C., Valentini R., Tiribelli N., other authors. 2010; Pandemic 2009 influenza A in Argentina: a study of 337 patients on mechanical ventilation. Am J Respir Crit Care Med 182:41–48 [View Article][PubMed]
    [Google Scholar]
  15. Fan J., Kapus A., Marsden P.A., Li Y.H., Oreopoulos G., Marshall J.C., Frantz S., Kelly R.A., Medzhitov R., Rotstein O.D. 2002; Regulation of Toll-like receptor 4 expression in the lung following hemorrhagic shock and lipopolysaccharide. J Immunol 168:5252–5259 [View Article][PubMed]
    [Google Scholar]
  16. Geiler J., Michaelis M., Naczk P., Leutz A., Langer K., Doerr H.W., Cinatl J. Jr 2010; N-Acetyl-l-cysteine (NAC) inhibits virus replication and expression of pro-inflammatory molecules in A549 cells infected with highly pathogenic H5N1 influenza A virus. Biochem Pharmacol 79:413–420 [View Article][PubMed]
    [Google Scholar]
  17. Guney Y., Turkcu U.O., Hicsonmez A., Andrieu M.N., Guney H.Z., Bilgihan A., Kurtman C. 2006; Carnosine may reduce lung injury caused by radiation therapy. Med Hypotheses 66:957–959 [View Article][PubMed]
    [Google Scholar]
  18. He G., Dong C., Luan Z., McAllan B.M., Xu T., Zhao L., Qiao J. 2013; Oxygen free radical involvement in acute lung injury induced by H5N1 virus in mice. Influenza Other Respi Viruses 7:945–953 [View Article][PubMed]
    [Google Scholar]
  19. Hien N.D., Ha N.H., Van N.T., Ha N.T., Lien T.T., Thai N.Q., Trang V.D., Shimbo T., Takahashi Y., other authors. 2009; Human infection with highly pathogenic avian influenza virus (H5N1) in northern Vietnam, 2004-2005. Emerg Infect Dis 15:19–23 [View Article][PubMed]
    [Google Scholar]
  20. Hou Y., Wang L., Yi D., Ding B., Yang Z., Li J., Chen X., Qiu Y., Wu G. 2013; N-Acetylcysteine reduces inflammation in the small intestine by regulating redox, EGF and TLR4 signaling. Amino Acids 45:513–522 [View Article][PubMed]
    [Google Scholar]
  21. Imai Y., Kuba K., Neely G.G., Yaghubian-Malhami R., Perkmann T., van Loo G., Ermolaeva M., Veldhuizen R., Leung Y.H., other authors. 2008; Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell 133:235–249 [View Article][PubMed]
    [Google Scholar]
  22. Khadaroo R.G., Marshall J.C. 2002; ARDS and the multiple organ dysfunction syndrome: common mechanisms of a common systemic process. Crit Care Clin 18:127–141 [View Article][PubMed]
    [Google Scholar]
  23. Kumar A. 2011; Pandemic H1N1 influenza. J Thorac Dis 3:262–270[PubMed]
    [Google Scholar]
  24. Lafferty E.I., Qureshi S.T., Schnare M. 2010; The role of Toll-like receptors in acute and chronic lung inflammation. J Inflamm (Lond) 7:57 [View Article][PubMed]
    [Google Scholar]
  25. Lang J.D., Figueroa M., Sanders K.D., Aslan M., Liu Y., Chumley P., Freeman B.A. 2005; Hypercapnia via reduced rate and tidal volume contributes to lipopolysaccharide-induced lung injury. Am J Respir Crit Care Med 171:147–157 [View Article][PubMed]
    [Google Scholar]
  26. Lee W.L., Downey G.P. 2001; Neutrophil activation and acute lung injury. Curr Opin Crit Care 7:1–7 [View Article][PubMed]
    [Google Scholar]
  27. Lee Y.S., Kang Y.S., Lee S.H., Kim J.A. 2000; Role of NAD(P)H oxidase in the tamoxifen-induced generation of reactive oxygen species and apoptosis in HepG2 human hepatoblastoma cells. Cell Death Differ 7:925–932 [View Article][PubMed]
    [Google Scholar]
  28. Lee Y.T., Hsu C.C., Lin M.H., Liu K.S., Yin M.C. 2005; Histidine and carnosine delay diabetic deterioration in mice and protect human low density lipoprotein against oxidation and glycation. Eur J Pharmacol 513:145–150 [View Article][PubMed]
    [Google Scholar]
  29. Lu X., Tumpey T.M., Morken T., Zaki S.R., Cox N.J., Katz J.M. 1999; A mouse model for the evaluation of pathogenesis and immunity to influenza A (H5N1) viruses isolated from humans. J Virol 73:5903–5911[PubMed]
    [Google Scholar]
  30. Majeski E.I., Paintlia M.K., Lopez A.D., Harley R.A., London S.D., London L. 2003; Respiratory reovirus 1/L induction of intraluminal fibrosis, a model of bronchiolitis obliterans organizing pneumonia, is dependent on T lymphocytes. Am J Pathol 163:1467–1479 [View Article][PubMed]
    [Google Scholar]
  31. Mata M., Sarrion I., Armengot M., Carda C., Martinez I., Melero J.A., Cortijo J. 2012; Respiratory syncytial virus inhibits ciliagenesis in differentiated normal human bronchial epithelial cells: effectiveness of N-acetylcysteine. PLoS One 7:e48037 [View Article][PubMed]
    [Google Scholar]
  32. Matthay M.A., Zemans R.L. 2011; The acute respiratory distress syndrome: pathogenesis and treatment. Annu Rev Pathol 6:147–163 [View Article][PubMed]
    [Google Scholar]
  33. Matthay M.A., Zimmerman G.A. 2005; Acute lung injury and the acute respiratory distress syndrome: four decades of inquiry into pathogenesis and rational management. Am J Respir Cell Mol Biol 33:319–327 [View Article][PubMed]
    [Google Scholar]
  34. Narasaraju T., Yang E., Samy R.P., Ng H.H., Poh W.P., Liew A.A., Phoon M.C., van Rooijen N., Chow V.T. 2011; Excessive neutrophils and neutrophil extracellular traps contribute to acute lung injury of influenza pneumonitis. Am J Pathol 179:199–210 [View Article][PubMed]
    [Google Scholar]
  35. Nencioni L., Iuvara A., Aquilano K., Ciriolo M.R., Cozzolino F., Rotilio G., Garaci E., Palamara A.T. 2003; Influenza A virus replication is dependent on an antioxidant pathway that involves GSH and Bcl-2. FASEB J 17:758–760[PubMed]
    [Google Scholar]
  36. Noori S., Mahboob T. 2010; Antioxidant effect of carnosine pretreatment on cisplatin-induced renal oxidative stress in rats. Indian J Clin Biochem 25:86–91 [View Article][PubMed]
    [Google Scholar]
  37. Parsey M.V., Tuder R.M., Abraham E. 1998; Neutrophils are major contributors to intraparenchymal lung IL-1β expression after hemorrhage and endotoxemia. J Immunol 160:1007–1013[PubMed]
    [Google Scholar]
  38. Peiris M., Yuen K.Y., Leung C.W., Chan K.H., Ip P.L., Lai R.W., Orr W.K., Shortridge K.F. 1999; Human infection with influenza H9N2. Lancet 354:916–917 [View Article][PubMed]
    [Google Scholar]
  39. Peiris J.S., Poon L.L., Guan Y. 2009; Emergence of a novel swine-origin influenza A virus (S-OIV) H1N1 virus in humans. J Clin Virol 45:169–173 [View Article][PubMed]
    [Google Scholar]
  40. Pinto R., Herold S., Cakarova L., Hoegner K., Lohmeyer J., Planz O., Pleschka S. 2011; Inhibition of influenza virus-induced NF-kappaB and Raf/MEK/ERK activation can reduce both virus titers and cytokine expression simultaneously in vitro and in vivo . Antiviral Res 92:45–56 [View Article][PubMed]
    [Google Scholar]
  41. Raghavendran K., Napolitano L.M. 2011; ALI and ARDS: challenges and advances. Crit Care Clin 27:xiii–xxiv [View Article][PubMed]
    [Google Scholar]
  42. Ryrfeldt A., Bannenberg G., Moldéus P. 1993; Free radicals and lung disease. Br Med Bull 49:588–603[PubMed]
    [Google Scholar]
  43. Salomon R., Hoffmann E., Webster R.G. 2007; Inhibition of the cytokine response does not protect against lethal H5N1 influenza infection. Proc Natl Acad Sci U S A 104:12479–12481 [View Article][PubMed]
    [Google Scholar]
  44. Sithisarn P., Michaelis M., Schubert-Zsilavecz M., Cinatl J. Jr 2013; Differential antiviral and anti-inflammatory mechanisms of the flavonoids biochanin A and baicalein in H5N1 influenza A virus-infected cells. Antiviral Res 97:41–48 [View Article][PubMed]
    [Google Scholar]
  45. Tran T.H., Nguyen T.L., Nguyen T.D., Luong T.S., Pham P.M., Nguyen V., Pham T.S., Vo C.D., Le T.Q., other authors. 2004; Avian influenza A (H5N1) in 10 patients in Vietnam. N Engl J Med 350:1179–1188 [View Article][PubMed]
    [Google Scholar]
  46. Vlahos R., Stambas J., Bozinovski S., Broughton B.R., Drummond G.R., Selemidis S. 2011; Inhibition of Nox2 oxidase activity ameliorates influenza A virus-induced lung inflammation. PLoS Pathog 7:e1001271 [View Article][PubMed]
    [Google Scholar]
  47. Vlahos R., Stambas J., Selemidis S. 2012; Suppressing production of reactive oxygen species (ROS) for influenza A virus therapy. Trends Pharmacol Sci 33:3–8 [View Article][PubMed]
    [Google Scholar]
  48. Wiwanitkit V. 2013; H7N9 influenza: the emerging infectious disease. N Am J Med Sci 5:395–398 [View Article][PubMed]
    [Google Scholar]
  49. Xiang M., Fan J., Fan J. 2010; Association of Toll-like receptor signaling and reactive oxygen species: a potential therapeutic target for posttrauma acute lung injury. Mediators Inflamm 2010:1–8 [View Article][PubMed]
    [Google Scholar]
  50. Xu T., Qiao J., Zhao L., Wang G., He G., Li K., Tian Y., Gao M., Wang J., other authors. 2006; Acute respiratory distress syndrome induced by avian influenza A (H5N1) virus in mice. Am J Respir Crit Care Med 174:1011–1017 [View Article][PubMed]
    [Google Scholar]
  51. Xu T., Qiao J., Zhao L., He G., Li K., Wang J., Tian Y., Wang H. 2009; Effect of dexamethasone on acute respiratory distress syndrome induced by the H5N1 virus in mice. Eur Respir J 33:852–860 [View Article][PubMed]
    [Google Scholar]
  52. Yu H., Gao Z., Feng Z., Shu Y., Xiang N., Zhou L., Huai Y., Feng L., Peng Z., other authors. 2008; Clinical characteristics of 26 human cases of highly pathogenic avian influenza A (H5N1) virus infection in China. PLoS One 3:e2985 [View Article][PubMed]
    [Google Scholar]
  53. Zhang R.H., Li C.H., Wang C.L., Xu M.J., Xu T., Wei D., Liu B.J., Wang G.H., Tian S.F. 2014; N-Acetyl-l-cystine (NAC) protects against H9N2 swine influenza virus-induced acute lung injury. Int Immunopharmacol 22:1–8 [View Article][PubMed]
    [Google Scholar]
  54. Zhang L., Li Y., Gu Z., Wang Y., Shi M., Ji Y., Sun J., Xu X., Zhang L., other authors. 2015; Resveratrol inhibits enterovirus 71 replication and pro-inflammatory cytokine secretion in rhabdosarcoma cells through blocking IKKs/NF-κB signaling pathway. PLoS One 10:e0116879 [View Article][PubMed]
    [Google Scholar]
  55. Ziegler-Heitbrock H.W., Sternsdorf T., Liese J., Belohradsky B., Weber C., Wedel A., Schreck R., Bäuerle P., Ströbel M. 1993; Pyrrolidine dithiocarbamate inhibits NF-kappa B mobilization and TNF production in human monocytes. J Immunol 151:6986–6993[PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.000238
Loading
/content/journal/jgv/10.1099/jgv.0.000238
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error