Skip to main content

Advertisement

Log in

Protective effects of antioxidant-fortified diet on renal function and metabolic profile in obese Zucker rat

  • Original Paper
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Oxidative stress contributes to the pathophysiology of type 2 diabetes mellitus and its complications, including nephropathy. The current study was designed to test the hypothesis that a diet fortified with antioxidants would be beneficial to delay or prevent the progression of this disease. Male and female Zucker fa/fa rats were fed a control or an antioxidant (AO)-fortified diet starting at 4 weeks of age. Metabolic parameters, renal function, and renal histopathology were analyzed at 6, 13, and 20 weeks of age. Females on the AO diet had significantly lower blood glucose at 6 and 13 weeks, less severe renal pathology at 20 weeks, and higher glomerular filtration rates (GFR) at 20 weeks than age-matched females on the regular diet (P < 0.05). Metabolic parameters including blood glucose, insulin resistance, and serum cholesterol, and mean arterial pressure (MAP), worsened with age in both males and females, as expected. GFR decreased and renal pathology also became more severe with age. Finally, females on the AO diet had higher GFRs and lower MAP at 20 weeks than males on the same diet. This may denote a protective effect of the AO diet in females, but not in males. These findings may have implications for the role of antioxidants as therapy in humans with T2DM.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. D.E. Moller, Nature 414, 821–827 (2001)

    Article  CAS  PubMed  Google Scholar 

  2. T.M. Coimbra, U. Janssen, H.J. Grone, T. Ostendorf, U. Kunter et al., Kidney Int. 57, 167–182 (2000)

    Article  CAS  PubMed  Google Scholar 

  3. B. Poirier, M. Lannaud-Bournoville, M. Conti, R. Bazin, O. Michel et al., Nephrol. Dial. Transplant. 15, 467–476 (2000)

    Article  CAS  PubMed  Google Scholar 

  4. E. Ionescu, J.F. Sauter, B. Jeanrenaud, Am. J. Physiol. 248, E500–E506 (1985)

    CAS  PubMed  Google Scholar 

  5. B.L. Kasiske, M.P. O’Donnell, W.F. Keane, Hypertension 19, I110–I115 (1992)

    CAS  PubMed  Google Scholar 

  6. B.D. Myers, West. J. Med. 145, 235–237 (1986)

    CAS  PubMed  Google Scholar 

  7. P.N. Chander, O. Gealekman, S.V. Brodsky, S. Elitok, A. Tojo et al., J. Am. Soc. Nephrol. 15, 2391–2403 (2004)

    Article  CAS  PubMed  Google Scholar 

  8. D. de Zeeuw, G. Remuzzi, H.H. Parving, W.F. Keane, Z. Zhang et al., Kidney Int. 65, 2309–2320 (2004)

    Article  PubMed  Google Scholar 

  9. R. Garza, R. Medina, S. Basu, J.A. Pugh, Am. J. Nephrol. 17, 59–67 (1997)

    Article  CAS  PubMed  Google Scholar 

  10. H.E. Resnick, B.V. Howard, Annu. Rev. Med. 53, 245–267 (2002)

    Article  CAS  PubMed  Google Scholar 

  11. J. Neugarten, J. Am. Soc. Nephrol. 13, 2807–2809 (2002)

    Article  PubMed  Google Scholar 

  12. M.D. Gades, J.S. Stern, H. van Goor, D. Nguyen, P.R. Johnson, G.A. Kaysen, Kidney Int. 53, 130–135 (1998)

    Article  CAS  PubMed  Google Scholar 

  13. F.T. Stevenson, C.M. Wheeldon, M.D. Gades, G.A. Kaysen, J.S. Stern, H. van Goor, Kidney Int. 57, 1927–1935 (2000)

    Article  CAS  PubMed  Google Scholar 

  14. S. Silbiger, J. Neugarten, Gend. Med. 5(Suppl A), S3–S10 (2008)

    Article  PubMed  Google Scholar 

  15. J. Vague, Am. J. Clin. Nutr. 4, 20–34 (1956)

    CAS  PubMed  Google Scholar 

  16. ERA, European Transplant and Dialysis Annual Report (2005)

  17. M. Asghar, E. Monjok, G. Kouamou, S.E. Ohia, D. Bagchi, M.F. Lokhandwala, Mol. Cell. Biochem. 304, 93–99 (2007)

    Article  CAS  PubMed  Google Scholar 

  18. S. Prabhakar, J. Starnes, S. Shi, B. Lonis, R. Tran, J. Am. Soc. Nephrol. 18, 2945–2952 (2007)

    Article  CAS  PubMed  Google Scholar 

  19. M. Kaneki, N. Shimizu, D. Yamada, K. Chang, Antioxid. Redox Signal. 9, 319–329 (2007)

    Article  CAS  PubMed  Google Scholar 

  20. R. Domenico, Curr. Pharm. Des. 10, 1667–1676 (2004)

    Article  CAS  PubMed  Google Scholar 

  21. T. Tomohiro, T. Kumai, T. Sato, Y. Takeba, S. Kobayashi, K. Kimura, Life Sci. 80, 1364–1372 (2007)

    Article  CAS  PubMed  Google Scholar 

  22. E.C. Opara, J. Investig. Med. 52, 19–23 (2004)

    CAS  PubMed  Google Scholar 

  23. S. Vega-Lopez, S. Devaraj, I. Jialal, J. Investig. Med. 52, 24–32 (2004)

    Article  CAS  PubMed  Google Scholar 

  24. D. Mekinova, V. Chorvathova, K. Volkovova, M. Staruchova, E. Grancicova, J. Klvanova, R. Ondreicka, Nahrung 39, 257–261 (1995)

    Article  CAS  PubMed  Google Scholar 

  25. J.R. Koo, N.D. Vaziri, Kidney Int. 63, 195–201 (2003)

    Article  CAS  PubMed  Google Scholar 

  26. S.J. Hamilton, G.T. Chew, G.F. Watts, Diab. Vasc. Dis. Res. 4, 89–102 (2007)

    Article  PubMed  Google Scholar 

  27. N.F. Wiernsperger, Biofactors 19, 11–18 (2003)

    Article  CAS  PubMed  Google Scholar 

  28. M.S. Phillips, Q. Liu, H.A. Hammond, V. Dugan, P.J. Hey et al., Nat. Genet. 13, 18–19 (1996)

    Article  CAS  PubMed  Google Scholar 

  29. D.Z. Levine, K.D. Burns, J. Jaffey, M. Iacovitti, Kidney Int. 65, 184–189 (2004)

    Article  CAS  PubMed  Google Scholar 

  30. B. Badzynska, M. Grzelec-Mojzesowicz, J. Sadowski, Acta Physiol. Scand. 182, 313–318 (2004)

    Article  CAS  PubMed  Google Scholar 

  31. Y. Moriwaki, T. Inokuchi, A. Yamamoto, T. Ka, Z. Tsutsumi et al., Acta Diabetol. 44, 215–218 (2007)

    Article  CAS  PubMed  Google Scholar 

  32. Z. Li, B. Rodriguez-Iturbe, Z. Ni, A. Shahkarami, L. Sepassi, N.D. Vaziri, Kidney Int. 68, 2766–2772 (2005)

    Article  CAS  PubMed  Google Scholar 

  33. R.H. Pichler, N. Franceschini, B.A. Young, C. Hugo, T.F. Andoh et al., J. Am. Soc. Nephrol. 6, 1186–1196 (1995)

    CAS  PubMed  Google Scholar 

  34. J.H. Zar, Biostatistical Analysis (Prentice Hall, Englewood Cliffs, NJ, 1984)

    Google Scholar 

  35. G.A. Bray, Fed. Proc. 36, 148–153 (1977)

    CAS  PubMed  Google Scholar 

  36. A.A. Ajayi, G.O. Ogungbade, A.O. Okorodudu, Eur. J. Clin. Invest. 34, 349–357 (2004)

    Article  CAS  PubMed  Google Scholar 

  37. B.L. Kasiske, M.P. Cleary, M.P. O’Donnell, W.F. Keane, J. Lab. Clin. Med. 106, 598–604 (1985)

    CAS  PubMed  Google Scholar 

  38. K.G. Alberti, P. Zimmet, J. Shaw, Diabet. Med. 23, 469–480 (2006)

    Article  CAS  PubMed  Google Scholar 

  39. A.J. Collins, B.L. Kasiske, C. Herzog et al., Am. J. Kidney Dis. 49, S1–S296 (2007)

    Article  Google Scholar 

  40. A.M. Verhagen, D.M. Attia, H.A. Koomans, J.A. Joles, Am. J. Physiol. Renal. Physiol. 279, F664–F670 (2000)

    CAS  PubMed  Google Scholar 

  41. G. Imai, T. Satoh, T. Kumai, M. Murao, H. Tsuchida et al., Hypertens. Res. 26, 339–347 (2003)

    Article  CAS  PubMed  Google Scholar 

  42. S. Riazi, V.K. Madala-Halagappa, X. Hu, C.A. Ecelbarger, Gend. Med. 3, 309–327 (2006)

    Article  PubMed  Google Scholar 

  43. A.J. Strohmayer, D. Greenberg, Physiol. Behav. 60, 273–275 (1996)

    Article  CAS  PubMed  Google Scholar 

  44. F. Svec, H. Thompson, C. Corll, J. Porter, Nutr. Neurosci. 5, 321–326 (2002)

    Article  CAS  PubMed  Google Scholar 

  45. I. Bogacka, D.S. Roane, X. Xi, J. Zhou, B. Li et al., Nutr. Neurosci. 7, 67–74 (2004)

    Article  CAS  PubMed  Google Scholar 

  46. A. Mooradian, F. Nowak, in Cardiovascular Disease in Older People, ed. by F. Kaiser, J. Morley, R. Coe (Springer Publishing Co., Inc, New York, NY, 1997), pp. 53–72

    Google Scholar 

  47. A.C. Maritim, R.A. Sanders, J.B. Watkins, J.B., Watkins 3rd, J. Biochem. Mol. Toxicol. 17, 24–38 (2003)

    Article  CAS  PubMed  Google Scholar 

  48. H.B. Lee, M.R. Yu, Y. Yang, Z. Jiang, H. Ha, J. Am. Soc. Nephrol. 14, S241–S245 (2003)

    Article  CAS  PubMed  Google Scholar 

  49. M. Satoh, S. Fujimoto, Y. Haruna, S. Arakawa, H. Horike et al., Am. J. Physiol. Renal. Physiol. 288, F1144–F1152 (2005)

    Article  CAS  PubMed  Google Scholar 

  50. D.W. Laight, K.M. Desai, N.K. Gopaul, E.E. Anggard, M.J. Carrier, Br. J. Pharmacol. 128, 269–271 (1999)

    Article  CAS  PubMed  Google Scholar 

  51. D.W. Laight, K.M. Desai, E.E. Anggard, M.J. Carrier, Eur. J. Pharmacol. 402, 95–99 (2000)

    Article  CAS  PubMed  Google Scholar 

  52. A. Ceriello, Diabetes Care. 26, 1589–1596 (2003)

    Article  CAS  PubMed  Google Scholar 

  53. J. Xu, Z. Xie, R. Reece, D. Pimental, M.H. Zou, Arterioscler. Thromb. Vasc. Biol. 26, 2688–2695 (2006)

    Article  CAS  PubMed  Google Scholar 

  54. J. Sun, L.J. Druhan, J.L. Zweier, Arch. Biochem. Biophys. 471, 126–133 (2008)

    Article  CAS  PubMed  Google Scholar 

  55. T. Thum, D. Fraccarollo, M. Schultheiss, S. Froese, P. Galuppo et al., Diabetes 56, 666–674 (2007)

    Article  CAS  PubMed  Google Scholar 

  56. S. Blakely, A. Herbert, M. Collins, M. Jenkins, G. Mitchell et al., J. Nutr. 133, 2838–2844 (2003)

    CAS  PubMed  Google Scholar 

  57. P. Faure, Clin. Chem. Lab. Med. 41, 995–998 (2003)

    Article  CAS  PubMed  Google Scholar 

  58. J.L. Evans, Indian J. Med. Res. 125, 355–372 (2007)

    CAS  PubMed  Google Scholar 

  59. J. Garrow, W. James, A. Ralph, Human Nutrition and Dietetics (Churchill Livingstone, New York, NY, 2002)

    Google Scholar 

  60. C. Douillet, A. Tabib, M. Bost, M. Accominotti, F. Borson-Chazot, M. Ciavatti, Proc. Soc. Exp. Biol. Med. 211, 323–331 (1996)

    CAS  PubMed  Google Scholar 

  61. M. Brownlee, Nature 414, 813–820 (2001)

    Article  CAS  PubMed  Google Scholar 

  62. S. Yim, A. Malhotra, A. Veves, Curr. Diab Rep. 7, 8–13 (2007)

    Article  CAS  PubMed  Google Scholar 

  63. G. Lastra, C. Manrique, Antioxid. Redox Signal. 9, 943–954 (2007)

    Article  CAS  PubMed  Google Scholar 

  64. A.L. Tan, J.M. Forbes, M.E. Cooper, Semin. Nephrol. 27, 130–143 (2007)

    Article  CAS  PubMed  Google Scholar 

  65. H.B. Lee, J.Y. Seo, M.R. Yu, S.T. Uh, H. Ha, Kidney Int. 72, S67–S70 (2007)

  66. D. Behne, A. Kyriakopoulos, Annu. Rev. Nutr. 21, 453–473 (2001)

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors wish to thank Victor Heh, Ph.D., in the OU-COM Office of Research and Grants for expert assistance with statistical analysis, and R. Balaji, M.S., and K. Coschigano, Ph.D., for critical reading of this manuscript. This work was supported by NIH Grant DK073066 to SRI and FVN and by the Diabetes Research Initiative of Ohio University to FVN. Graphical and illustration assistance was provided by the OU-COM Office of Communications.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Felicia V. Nowak.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Slyvka, Y., Inman, S.R., Malgor, R. et al. Protective effects of antioxidant-fortified diet on renal function and metabolic profile in obese Zucker rat. Endocr 35, 89–100 (2009). https://doi.org/10.1007/s12020-008-9121-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-008-9121-7

Keywords

Navigation