Biochemistry (Moscow)

, Volume 79, Issue 5, pp 450–458

Ozone ameliorates age-related oxidative stress changes in rat liver and kidney: Effects of pre- and post-ageing administration

  • M. H. Safwat
  • M. M. El-Sawalhi
  • M. N. Mausouf
  • A. A. Shaheen


The ageing process is known to be accompanied by increased oxidative stress and compromised antioxidant defenses. Controlled ozone administration has been shown to be effective in various pathophysiological conditions with an underlying oxidative burden. However, its effect on the biochemical alterations associated with the ageing process has been rarely studied. Therefore, the present work was carried out to study the role of ozone in counteracting the state of oxidative stress associated with ageing in rat liver and kidneys using two experimental models. In the pre-ageing model, ozone was administered prior to the onset of ageing at adulthood and continued after the start of the ageing process (3-month-old rats until the age of 15 months). While in the post-ageing model, ozone was administered after ageing has begun and lasted for one month (14-month-old rats until the age of 15 months). The pre-ageing ozone administration effectively reduced lipid and protein oxidation markers, namely, malondialdehyde and protein carbonyl levels and decreased lipofuscin pigment deposition in rat liver and kidneys. Moreover, it significantly restored hepatic and renal reduced glutathione (GSH) contents and normalized cytosolic hepatic glutathione peroxidase activity. Similar but less pronounced effects were observed in the post-ageing ozone-treated group. Nevertheless, in the latter model ozone administration failed to significantly affect liver and kidney lipofuscin levels, as well as kidney GSH contents. These data provide evidences for potentially positive effects of pre-ageing ozone therapy in neutralizing chronic oxidative stress associated with ageing in rat liver and kidneys.

Key words

ozone oxidative stress liver kidney pre-ageing post-ageing 



glutathione peroxidase


reduced glutathione




reactive oxygen species


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  1. 1.
    Subathra, M., Shila, S., Devi, M. A., and Panneerselvam, C. (2005) Exp. Gerontol., 40, 707–715.PubMedCrossRefGoogle Scholar
  2. 2.
    Fontana, L., and Klein, S. (2007) JAMA, 297, 986–994.PubMedCrossRefGoogle Scholar
  3. 3.
    Kirkwood, T. (2008) Nature, 451, 644–647.PubMedCrossRefGoogle Scholar
  4. 4.
    Hayflick, L. (2007) Ann. N. Y. Acad. Sci., 1100, 1–13.PubMedCrossRefGoogle Scholar
  5. 5.
    Gil, L. (2011) Biomed. Ageing Pathol., 1, 1–7.CrossRefGoogle Scholar
  6. 6.
    Gemma, J., Bachstetter, A., and Bickford, P. (2007) in Brain Ageing: Models, Methods, and Mechanisms (Riddle, D., ed.) 1st Edn., CRC Press, London-New York, pp. 353–374.Google Scholar
  7. 7.
    Hagen, T. M. (2003) Antioxid. Redox Signal., 5, 503–506.PubMedCrossRefGoogle Scholar
  8. 8.
    Barja, G., Cadenas, S., Rojas, C., Lopez-Torres, M., and Perez-Campo, R. (1994) Comp. Biochem. Physiol. Biochem. Mol. Biol., 108, 501–512.PubMedCrossRefGoogle Scholar
  9. 9.
    Droge, W., and Schipper, H. M. (2007) Ageing Cell, 6, 361–370.CrossRefGoogle Scholar
  10. 10.
    Schmucker, D. L. (1998) J. Gerontol., 53, 315–320.CrossRefGoogle Scholar
  11. 11.
    Jung, K., and Henke, W. (1996) Free Radic. Biol. Med., 20, 613–617.PubMedCrossRefGoogle Scholar
  12. 12.
    Lebel, M., de Souza-Pinto, N. C., and Bohr, V. A. (2011) Curr. Gerontol. Geriatr. Res., 2011, 859415–859429.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Clark, B. (2000) Adv. Ren. Replace Ther., 7, 11–21.PubMedGoogle Scholar
  14. 14.
    Percy, C. J., Brown, L., Power, D. A., Johnson, D. W., and Gobe, G. C. (2009) Mech. Ageing Dev., 130, 129–138.PubMedCrossRefGoogle Scholar
  15. 15.
    Uribarri, J., Peppa, M., Cai, W., Goldberg, T., Lu, M., He, C., and Vlassara, H. (2003) J. Am. Soc. Nephrol., 14, 728–731.PubMedCrossRefGoogle Scholar
  16. 16.
    Gomes, P., Simao, S., Silva, E., Pinto, V., Amaral, J. S., Afonso, J., Serrao, M. P., Pinho, M. J., and Soares-da-Silva, P. (2009) Oxid. Med. Cell Longev., 2, 138–145.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Uribarri, J., Stirban, A., Sander, D., Cai, W., Negrean, M., Buenting, C. E., Koschinsky, T., and Vlassara, H. (2007) Diabetes Care, 30, 2579–2582.PubMedCrossRefGoogle Scholar
  18. 18.
    Negre-Salvayre, A., Auge, N., Ayala, V., Basaga, H., Boada, J., Brenke, R., Chapple, S., Cohen, G., Feher, J., Grune, T., Lengyel, G., Mann, G. E., Pamplona, R., Poli, G., Portero-Otin, M., Riahi, Y., Salvayre, R., Sasson, S., Serrano, J., Shamni, D., Siems, W., Siow, R. C., Wiswedel, I., Zarkovic, K., and Zarkovic, N. (2010) Free Radic. Res., 44, 1125–1171.PubMedCrossRefGoogle Scholar
  19. 19.
    Bocci, V., Borrelli, E., Travagli, V., and Zanardi, I. (2009) Med. Res. Rev., 29, 646–682.PubMedCrossRefGoogle Scholar
  20. 20.
    Borrego, A., Zamora, Z. B., Gonzalez, R., Romay, C., Menendez, S., Hernandez, F., Montero, T., and Rojas, E. (2004) Mediators Inflamm., 13, 13–19.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Ajamieh, H. H., Menendez, S., Martinez-Sanchez, G., Candelario-Jalil, E., Re, L., Giuliani, A., and Fernandez, O. S. (2004) Liver Int., 24, 55–62.PubMedCrossRefGoogle Scholar
  22. 22.
    Chen, H., Xing, B., Liu, X., Zhan, B., Zhou, J., Zhu, H., and Chen, Z. (2008) Arch. Med. Res., 39, 169–178.PubMedCrossRefGoogle Scholar
  23. 23.
    Morsy, M. D., Hassan, W. N., and Zalat, S. I. (2010) Diabetol. Metab. Syndr., 2, 29–35.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Martinez-Sanchez, G., Delgado-Roche, L., Diaz-Batista, A., Perez-Davison, G., and Re, L. (2012) Eur. J. Pharmacol., 691, 156–162.PubMedCrossRefGoogle Scholar
  25. 25.
    Shehata, N. I., Abd-Elgawad, H. M., Mawsouf, M. N., and Shaheen, A. A. (2012) Biogerontology, 13, 565–581.PubMedCrossRefGoogle Scholar
  26. 26.
    El-Sawalhi, M. M., Darwish, H. A., Mausouf, M. N., and Shaheen, A. A. (2013) Cell Biochem. Funct., 31, 518–525.PubMedCrossRefGoogle Scholar
  27. 27.
    Sharman, E. H., and Bondy, S. C. (2001) Neurobiol. Ageing, 22, 629–634.CrossRefGoogle Scholar
  28. 28.
    Gonzalez, R., Borrego, A., Zamora, Z., Romay, C., Hernandez, F., Menendez, S., Montero, T., and Rojas, E. (2004) Mediators Inflamm., 13, 307–312.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Re, L., Mawsouf, M. N., Menendez, S., Leon, O. S., Sanchez, G. M., and Hernandez, F. (2008) Arch. Med. Res., 39, 17–26.PubMedCrossRefGoogle Scholar
  30. 30.
    Mihara, M., and Uchiyama, M. (1978) Anal. Biochem., 86, 271–278.PubMedCrossRefGoogle Scholar
  31. 31.
    Reznick, A. Z., and Packer, L. (1994) Methods Enzymol., 233, 357–363.PubMedCrossRefGoogle Scholar
  32. 32.
    Liu, R., Liu, I. Y., Bi, X., Thompson, R. F., Doctrow, S. R., Malfroy, B., and Baudry, M. (2003) Proc. Natl. Acad. Sci. USA, 100, 8526–8531.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Abd El Mohsen, M. M., Iravani, M. M., Spencer, J. P., Rose, S., Fahim, A. T., Motawi, T. M., Ismail, N. A., and Jenner, P. (2005) Biochem. Biophys. Res. Commun., 336, 386–391.PubMedCrossRefGoogle Scholar
  34. 34.
    Tappel, A., Fletcher, B., and Deamer, D. (1973) J. Gerontol., 28, 415–424.PubMedCrossRefGoogle Scholar
  35. 35.
    Beutler, E., Duron, O., and Kelly, B. M. (1963) J. Lab. Clin. Med., 61, 882–888.PubMedGoogle Scholar
  36. 36.
    Paglia, D. E., and Valentine, W. N. (1967) J. Lab. Clin. Med., 70, 158–169.PubMedGoogle Scholar
  37. 37.
    Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. (1951) J. Biol. Chem., 193, 265–275.PubMedGoogle Scholar
  38. 38.
    Ramesh, T., Yoo, S. K., Kim, S. W., Hwang, S. Y., Sohn, S. H., Kim, I. W., and Kim, S. K. (2012) Exp. Gerontol., 47, 979–987.PubMedCrossRefGoogle Scholar
  39. 39.
    Harman, D. (1994) Ann. N. Y. Acad. Sci., 717, 1–15.PubMedCrossRefGoogle Scholar
  40. 40.
    Pandey, K. B., and Rizvi, S. I. (2010) Oxid. Med. Cell Longev., 3, 2–12.PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Tamburini, I., Quartacci, M. F., Izzo, R., and Bergamini, E. (2004) Ageing Clin. Exp. Res., 16, 425–431.CrossRefGoogle Scholar
  42. 42.
    Berrougui, H., and Khalil, A. (2009) Rejuvenation Res., 12, 117–126.PubMedCrossRefGoogle Scholar
  43. 43.
    Goto, S., Hasegawa, A., Nakamoto, H., Nakamura, A., Takahashi, R., and Kurochkin, I. V. (1995) in Oxidative Stress and Ageing (Cutler, R. C., et al., ed.) 1st Edn., Birkhauser, Basel, Switzerland, pp. 151–158.Google Scholar
  44. 44.
    Sohal, R. S. (2002) Free Radic. Biol. Med., 33, 37–44.PubMedCrossRefGoogle Scholar
  45. 45.
    Gruber, J., Ng, L. F., Fong, S., Wong, Y. T., Koh, S. A., Chen, C. B., Shui, G., Cheong, W. F., Schaffer, S., Wenk, M. R., and Halliwell, B. (2011) PLoS One, 6, e19444–19459.PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Petropoulos, I., Conconi, M., Wang, X., Hoenel, B., Bregegere, F., Milner, Y., and Friguet, B. (2000) J. Gerontol., 55, 220–227.CrossRefGoogle Scholar
  47. 47.
    Farout, L., and Friguet, B. (2006) Antioxid. Redox Signal., 8, 205–216.PubMedCrossRefGoogle Scholar
  48. 48.
    Kumar, P., Kale, R. K., and Baquer, N. Z. (2011) J. Ageing Res., 2011, 580245–580252.Google Scholar
  49. 49.
    Uribarri, J., Cai, W., Peppa, M., Goodman, S., Ferrucci, L., Striker, G., and Vlassara, H. (2007) J. Gerontol. A Biol. Sci. Med. Sci., 62, 427–433.PubMedCentralPubMedCrossRefGoogle Scholar
  50. 50.
    Hohn, A., Jung, T., Grimm, S., and Grune, T. (2010) Free Radic. Biol. Med., 48, 1100–1108.PubMedCrossRefGoogle Scholar
  51. 51.
    Shimizu, I., and Ito, S. (2007) Hepatol. Res., 37, 239–247.PubMedCrossRefGoogle Scholar
  52. 52.
    Rebrin, I., and Sohal, R. S. (2008) Adv. Drug Deliv. Rev., 60, 1545–1552.PubMedCentralPubMedCrossRefGoogle Scholar
  53. 53.
    Toroser, D., and Sohal, R. S. (2007) Biochem. J., 405, 583–589.PubMedCentralPubMedCrossRefGoogle Scholar
  54. 54.
    Sanz, N., Diez-Fernandez, C., Alvarez, A., and Cascales, M. (1997) J. Hepatol., 27, 525–534.PubMedCrossRefGoogle Scholar
  55. 55.
    Zubkova, E. V., and Robaire, B. (2004) Biol. Reprod., 71, 1002–1008.PubMedCrossRefGoogle Scholar
  56. 56.
    Tian, L., Cai, Q., and Wei, H. (1998) Free Radic. Biol. Med., 24, 1477–1484.PubMedCrossRefGoogle Scholar
  57. 57.
    Alabarse, P. V., Salomon, T. B., Medeiros, T. M., Hackenhaar, F. S., Schuller, A. K., Ehrenbrink, G., and Benfato, M. S. (2011) Exp. Gerontol., 46, 773–780.PubMedCrossRefGoogle Scholar
  58. 58.
    Ramesh, T., Kim, S. W., Sung, J. H., Hwang, S. Y., Sohn, S. H., Yoo, S. K., and Kim, S. K. (2012) Exp. Gerontol., 47, 77–84.PubMedCrossRefGoogle Scholar
  59. 59.
    Candelario-Jalil, E., Mohammed-Al-Dalain, S., Fernandez, O. S., Menendez, S., Perez-Davison, G., Merino, N., Sam, S., and Ajamieh, H. H. (2001) J. Appl. Toxicol., 21, 297–301.PubMedCrossRefGoogle Scholar
  60. 60.
    Bocci, V. (2007) Arch. Med. Res., 38, 265–267.PubMedCrossRefGoogle Scholar
  61. 61.
    Bocci, V., Borrelli, E., Corradeschi, F., and Valacchi, G. (2000) Int. J. Med. Biol. Environ., 28, 109–113.Google Scholar
  62. 62.
    Berlett, B. S., and Stadtman, E. R. (1997) J. Biol. Chem., 272, 20313–20316.PubMedCrossRefGoogle Scholar
  63. 63.
    Bocci, V., Aldinucci, C., Mosci, F., Carraro, F., and Valacchi, G. (2007) Mediators Inflamm., 16, 26785–26790.Google Scholar
  64. 64.
    Ajamieh, H., Berlanga, J., Merino, N., Sanchez, G. M., Carmona, A. M., Cepero, S. M., Giuliani, A., Re, L., and Leon, O. S. (2005) Transpl. Int., 18, 604–612.PubMedCrossRefGoogle Scholar
  65. 65.
    Iles, K. E., and Liu, R. M. (2005) Free Radic. Biol. Med., 38, 547–556.PubMedCrossRefGoogle Scholar
  66. 66.
    Hohn, A., Jung, T., Grimm, S., Catalgol, B., Weber, D., and Grune, T. (2011) Free Radic. Biol. Med., 50, 585–591.PubMedCrossRefGoogle Scholar
  67. 67.
    Shringarpure, R., Grune, T., Sitte, N., and Davies, K. J. (2000) Cell Mol. Life Sci., 57, 1802–1809.PubMedCrossRefGoogle Scholar
  68. 68.
    Ijichi, H., Taketomi, A., Yoshizumi, T., Uchiyama, H., Yonemura, Y., Soejima, Y., Shimada, M., and Maehara, Y. (2006) J. Hepatol., 45, 28–34.PubMedCrossRefGoogle Scholar
  69. 69.
    He, X., Xu, X., Fan, M., Chen, X., Sun, X., Luo, G., Chen, L., Mu, Q., Feng, Y., Mao, Q., and Chao, Z. (2011) J. Surg. Res., 170, 271–277.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2014

Authors and Affiliations

  • M. H. Safwat
    • 1
  • M. M. El-Sawalhi
    • 1
  • M. N. Mausouf
    • 2
  • A. A. Shaheen
    • 1
  1. 1.Biochemistry Department, Faculty of PharmacyCairo UniversityCairoEgypt
  2. 2.Ozone Therapy Unit, National Cancer InstituteCairo UniversityCairoEgypt

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