, Volume 33, Issue 3, pp 166–172 | Cite as

Therapeutic Effect of Recombinant Human Catalase on H1N1 Influenza-induced Pneumonia in Mice



Reactive oxygen species (ROS) are believed to play a key role in the induction of lung damage caused by pneumonia and therapeutic agents that could effectively scavenge ROS may prevent or reduce the deleterious effects of influenza-induced pneumonia. In this study, we first demonstrated that human catalase could attenuate acute oxidative injury in lung tissues following influenza-induced pneumonia. Mice were infected with influenza virus H1N1 (FM1 strain) and treated with recombinant human catalase (50,000 U/kg) by inhalation. The survival time and survival rates of H1N1 induced pneumonia mice were increased by treatment with recombinant human catalase. Protective efficacy of catalase was also observed in lung histology, anti-oxidant parameters, pulmonary pathology and influenza viral titer in lungs in mice. These observations were associated with increased serum superoxide and hydroxyl radical anion scavenging capacities. This study strongly indicated that recombinant catalase might be a potential therapy for H1N1 influenza-induced pneumonia.


human catalase influenza pneumonia oxidative injury 



This work was supported by grants from the National Nature Science Foundation of China (No: 30572276, 2006–2008), Shanghai Science and Technology Funds (No: 09XD1421800, 06DZ22906) and National Science and Technology Major Project for Drug Discovery of Ministry of Science and Technology of China (2009ZX09303).


  1. 1.
    Wang, C.C., K.M. Fang, C.S. Yang, and S.F. Tzeng. 2009. Reactive oxygen species-induced cell death of rat primary astrocytes through mitochondria-mediated mechanism. J Cell Biochem 107: 933–943.CrossRefPubMedGoogle Scholar
  2. 2.
    Khandrika, L., B. Kumar, S. Koul, P. Maroni, and H.K. Koul. 2009. Oxidative stress in prostate cancer. Cancer Lett 282: 125–136.CrossRefPubMedGoogle Scholar
  3. 3.
    Minelli, A., I. Bellezza, C. Conte, and Z. Culig. 2009. Oxidative stress-related aging: A role for prostate cancer? Biochim Biophys Acta 1795: 83–91.PubMedGoogle Scholar
  4. 4.
    Angelopoulou, R., G. Lavranos, and P. Manolakou. 2009. ROS in the aging male: Model diseases with ROS-related pathophysiology. Reprod Toxicol 28: 167–171.CrossRefPubMedGoogle Scholar
  5. 5.
    Lü, Z.M., L.Y. Sang, Z.M. Li, and H. Min. 2009. Catalase and superoxide dismutase activities in a Stenotrophomonas maltophilia WZ2 resistant to herbicide pollution. Ecotoxicol Environ Saf 72: 136–143.CrossRefPubMedGoogle Scholar
  6. 6.
    Ogbeyalu, E.O., E.J. George, Y.F. Zhao, L.C. Zhou, H. Yang, and Z.M. Guo. 2009. Overexpression of catalase delays G0/G1- to S-phase transition during cell cycle progression in mouse aortic endothelial cells. Free Radic Biol Med 46: 1658–1667.CrossRefGoogle Scholar
  7. 7.
    Brian, J.D. 2009. Catalase and glutathione peroxidase mimics. Biochem Pharmacol 77: 285–296.CrossRefGoogle Scholar
  8. 8.
    Tetsuro, Y., S. Yoshihiro, I. Toshio, N. Osamu, and R. Chisei. 2006. Silver activates mast cells through reactive oxygen species production and a thiol-sensitive store-independent Ca2+ influx. Free Radic Biol Med 40: 1949–1959.CrossRefGoogle Scholar
  9. 9.
    Bhalchandra, J.K., P. Anson, and D. Ladislav. 2007. Chronic hyperbaric oxygen treatment elicits an anti-oxidant response and attenuates atherosclerosis in apoE knockout mice. Atherosclerosis 193: 28–35.CrossRefGoogle Scholar
  10. 10.
    Tomochika, H., A. Shoichiro, W. Taiji, O. Shigeru, and K. Hiroyoshi. 2009. Protective effects of the complex between manganese porphyrins and catalase-poly(ethylene glycol) conjugates against hepatic ischemia/reperfusion injury in vivo. J Control Release 135: 60–64.CrossRefGoogle Scholar
  11. 11.
    Grace, Y., K.H. David, Y.D. Kira, R. Julie, G.H. Paul, T.C. John, and B.L. David. 2008. Focus on FOCIS: The continuing diagnostic challenge of autosomal recessive chronic granulomatous disease. Clin Immunol 128: 117–126.CrossRefGoogle Scholar
  12. 12.
    Makiya, N., H. Mitsuru, and T. Yoshinobu. 2009. Catalase delivery for inhibiting ROS-mediated tissue injury and tumor metastasis. Adv Drug Deliver Rev 61: 319–326.CrossRefGoogle Scholar
  13. 13.
    Hyoudou, K., M. Nishikawa, Y. Umeyama, Y. Kobayashi, F. Yamashita, and M. Hashida. 2004. Inhibition of metastatic tumor growth in mouse lung by repeated administration of polyethylene glycol-conjugated catalase: Quantitative analysis with firefly luciferase-expressing melanoma cells. Clin Cancer Res 10: 7685–7691.CrossRefPubMedGoogle Scholar
  14. 14.
    Derek, G. 2009. The 2009 H1N1 influenza outbreak in its historical context. J Clin Virol 45: 174–178.CrossRefGoogle Scholar
  15. 15.
    Taubenberger, J.K., and D.M. Morens. 2008. The pathology of influenza virus infections. Annu Rev Pathol 3: 499–522.CrossRefPubMedGoogle Scholar
  16. 16.
    Shi, X.L., M.Q. Feng, J. Shi, Z.H. Shi, J. Zhong, and P. Zhou. 2007. High-level expression and purification of recombinant human catalase in Pichia pastoris. Protein Expr Purif 54: 24–29.CrossRefPubMedGoogle Scholar
  17. 17.
    Jin, H., S. Manetz, J. Leininger, C. Luke, K. Subbarao, B. Murphy, G. Kemble, and K.L. Coelingh. 2007. Toxicological evaluation of live attenuated, cold-adapted H5N1 vaccines in ferrets. Vaccine 25: 8664–8672.CrossRefPubMedGoogle Scholar
  18. 18.
    Tao, P., M.C. Luo, R.G. Pan, D.W. Ling, S.Y. Zhou, P. Tien, and Z.S. Pan. 2009. Enhanced protective immunity against H5N1 influenza virus challenge by vaccination with DNA expressing a chimeric hemagglutinin in combination with an MHC class I-restricted epitope of nucleoprotein in mice. Antiv Res 81: 253–260.CrossRefGoogle Scholar
  19. 19.
    Wang, J.X., J.Y. Zhou, Q.W. Yang, Y. Chen, X. Li, Y.A. Piao, and H.Y. Li. 2008. An improved embryonated chicken egg model for the evaluation of antiviral drugs against influenza A virus. J Virol Methods 153: 218–222.CrossRefPubMedGoogle Scholar
  20. 20.
    World Health Organization Weekly Epidemiological Record. 2009. Global influenza surveillance network: laboratory surveillance and response to pandemic H1N1 2009. 84: 361–372.Google Scholar
  21. 21.
    Fraser, C., C.A. Donnelly, S. Cauchemez, W.P. Hanage, M.D. Van Kerkhove, T.D. Hollingsworth, J. Griffin, R.F. Baggaley, H.E. Jenkins, E.J. Lyons, T. Jombart, W.R. Hinsley, N.C. Grassly, F. Balloux, A.C. Ghani, N.M. Ferguson, A. Rambaut, O.G. Pybus, H. Lopez-Gatell, C.M. Alpuche-Aranda, I.B. Chapela, E.P. Zavala, D.M. Espejo Guevara, F. Checchi, E. Garcia, S. Hugonnet, and C. Roth. 2009. Pandemic potential of a strain of Influenza A (H1N1): Early findings. Science 324: 1557–1561.CrossRefPubMedGoogle Scholar
  22. 22.
    Taia, T.W., and P. Peter. 2009. Unraveling the mystery of swine influenza virus. Cell 137: 983–985.CrossRefGoogle Scholar
  23. 23.
    Imai, Y., K. Kuba, G.G. Neely, R. Yaghubian-Malhami, T. Perkmann, G. van Loo, M. Ermolaeva, R. Veldhuizen, Y.H.C. Leung, and H.L. Wang. 2008. Identification of oxidative stress and toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell 133: 235–249.CrossRefPubMedGoogle Scholar
  24. 24.
    Takayuki, N., K. Shigeru, Y. Fumiyoshi, and H. Mitsuru. 2007. Efficient protection by cationized catalase against H2O2 injury in primary cultured alveolar epithelial cells. J Control Release 121: 74–80.CrossRefGoogle Scholar
  25. 25.
    Dympna, M.P., E.Z. Tahereh, R. John, O.A. Ali, J. Mohammad, U. Luis, J.M. Edmund, and L.M. Lin. 2007. Antioxidants preserve macrophage phagocytosis of pseudomonas aeruginosa during hyperoxia. Free Radic Biol Med 42: 1338–1349.CrossRefGoogle Scholar
  26. 26.
    Kim, D.W., H.J. Jeong, H.W. Kang, M.J. Shin, E.J. Sohn, M.J. Kim, E.H. Ahn, J.J. An, S.H. Jang, K.Y. Yoo, M.H. Won, T.C. Kang, I.K. Hwang, O.S. Kwon, S.W. Cho, J. Park, W.S. Eum, and S.Y. Choi. 2009. Transduced human PEP-1-catalase fusion protein attenuates ischemic neuronal damage. Free Radic Biol Med 47: 941–952.CrossRefPubMedGoogle Scholar
  27. 27.
    Jian, W., G.H. James, and C. Nipavan. 2009. Antioxidant enzyme gene transfer for ischemic diseases. Adv Drug Deliver Rev 61: 351–363.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Biosynthesis, School of PharmacyFudan UniversityShanghaiChina
  2. 2.Department of Pathology, Shanghai Medical CollegeFudan UniversityShanghaiChina

Personalised recommendations