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.
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D.E. Moller, Nature 414, 821–827 (2001)
T.M. Coimbra, U. Janssen, H.J. Grone, T. Ostendorf, U. Kunter et al., Kidney Int. 57, 167–182 (2000)
B. Poirier, M. Lannaud-Bournoville, M. Conti, R. Bazin, O. Michel et al., Nephrol. Dial. Transplant. 15, 467–476 (2000)
E. Ionescu, J.F. Sauter, B. Jeanrenaud, Am. J. Physiol. 248, E500–E506 (1985)
B.L. Kasiske, M.P. O’Donnell, W.F. Keane, Hypertension 19, I110–I115 (1992)
B.D. Myers, West. J. Med. 145, 235–237 (1986)
P.N. Chander, O. Gealekman, S.V. Brodsky, S. Elitok, A. Tojo et al., J. Am. Soc. Nephrol. 15, 2391–2403 (2004)
D. de Zeeuw, G. Remuzzi, H.H. Parving, W.F. Keane, Z. Zhang et al., Kidney Int. 65, 2309–2320 (2004)
R. Garza, R. Medina, S. Basu, J.A. Pugh, Am. J. Nephrol. 17, 59–67 (1997)
H.E. Resnick, B.V. Howard, Annu. Rev. Med. 53, 245–267 (2002)
J. Neugarten, J. Am. Soc. Nephrol. 13, 2807–2809 (2002)
M.D. Gades, J.S. Stern, H. van Goor, D. Nguyen, P.R. Johnson, G.A. Kaysen, Kidney Int. 53, 130–135 (1998)
F.T. Stevenson, C.M. Wheeldon, M.D. Gades, G.A. Kaysen, J.S. Stern, H. van Goor, Kidney Int. 57, 1927–1935 (2000)
S. Silbiger, J. Neugarten, Gend. Med. 5(Suppl A), S3–S10 (2008)
J. Vague, Am. J. Clin. Nutr. 4, 20–34 (1956)
ERA, European Transplant and Dialysis Annual Report (2005)
M. Asghar, E. Monjok, G. Kouamou, S.E. Ohia, D. Bagchi, M.F. Lokhandwala, Mol. Cell. Biochem. 304, 93–99 (2007)
S. Prabhakar, J. Starnes, S. Shi, B. Lonis, R. Tran, J. Am. Soc. Nephrol. 18, 2945–2952 (2007)
M. Kaneki, N. Shimizu, D. Yamada, K. Chang, Antioxid. Redox Signal. 9, 319–329 (2007)
R. Domenico, Curr. Pharm. Des. 10, 1667–1676 (2004)
T. Tomohiro, T. Kumai, T. Sato, Y. Takeba, S. Kobayashi, K. Kimura, Life Sci. 80, 1364–1372 (2007)
E.C. Opara, J. Investig. Med. 52, 19–23 (2004)
S. Vega-Lopez, S. Devaraj, I. Jialal, J. Investig. Med. 52, 24–32 (2004)
D. Mekinova, V. Chorvathova, K. Volkovova, M. Staruchova, E. Grancicova, J. Klvanova, R. Ondreicka, Nahrung 39, 257–261 (1995)
J.R. Koo, N.D. Vaziri, Kidney Int. 63, 195–201 (2003)
S.J. Hamilton, G.T. Chew, G.F. Watts, Diab. Vasc. Dis. Res. 4, 89–102 (2007)
N.F. Wiernsperger, Biofactors 19, 11–18 (2003)
M.S. Phillips, Q. Liu, H.A. Hammond, V. Dugan, P.J. Hey et al., Nat. Genet. 13, 18–19 (1996)
D.Z. Levine, K.D. Burns, J. Jaffey, M. Iacovitti, Kidney Int. 65, 184–189 (2004)
B. Badzynska, M. Grzelec-Mojzesowicz, J. Sadowski, Acta Physiol. Scand. 182, 313–318 (2004)
Y. Moriwaki, T. Inokuchi, A. Yamamoto, T. Ka, Z. Tsutsumi et al., Acta Diabetol. 44, 215–218 (2007)
Z. Li, B. Rodriguez-Iturbe, Z. Ni, A. Shahkarami, L. Sepassi, N.D. Vaziri, Kidney Int. 68, 2766–2772 (2005)
R.H. Pichler, N. Franceschini, B.A. Young, C. Hugo, T.F. Andoh et al., J. Am. Soc. Nephrol. 6, 1186–1196 (1995)
J.H. Zar, Biostatistical Analysis (Prentice Hall, Englewood Cliffs, NJ, 1984)
G.A. Bray, Fed. Proc. 36, 148–153 (1977)
A.A. Ajayi, G.O. Ogungbade, A.O. Okorodudu, Eur. J. Clin. Invest. 34, 349–357 (2004)
B.L. Kasiske, M.P. Cleary, M.P. O’Donnell, W.F. Keane, J. Lab. Clin. Med. 106, 598–604 (1985)
K.G. Alberti, P. Zimmet, J. Shaw, Diabet. Med. 23, 469–480 (2006)
A.J. Collins, B.L. Kasiske, C. Herzog et al., Am. J. Kidney Dis. 49, S1–S296 (2007)
A.M. Verhagen, D.M. Attia, H.A. Koomans, J.A. Joles, Am. J. Physiol. Renal. Physiol. 279, F664–F670 (2000)
G. Imai, T. Satoh, T. Kumai, M. Murao, H. Tsuchida et al., Hypertens. Res. 26, 339–347 (2003)
S. Riazi, V.K. Madala-Halagappa, X. Hu, C.A. Ecelbarger, Gend. Med. 3, 309–327 (2006)
A.J. Strohmayer, D. Greenberg, Physiol. Behav. 60, 273–275 (1996)
F. Svec, H. Thompson, C. Corll, J. Porter, Nutr. Neurosci. 5, 321–326 (2002)
I. Bogacka, D.S. Roane, X. Xi, J. Zhou, B. Li et al., Nutr. Neurosci. 7, 67–74 (2004)
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
A.C. Maritim, R.A. Sanders, J.B. Watkins, J.B., Watkins 3rd, J. Biochem. Mol. Toxicol. 17, 24–38 (2003)
H.B. Lee, M.R. Yu, Y. Yang, Z. Jiang, H. Ha, J. Am. Soc. Nephrol. 14, S241–S245 (2003)
M. Satoh, S. Fujimoto, Y. Haruna, S. Arakawa, H. Horike et al., Am. J. Physiol. Renal. Physiol. 288, F1144–F1152 (2005)
D.W. Laight, K.M. Desai, N.K. Gopaul, E.E. Anggard, M.J. Carrier, Br. J. Pharmacol. 128, 269–271 (1999)
D.W. Laight, K.M. Desai, E.E. Anggard, M.J. Carrier, Eur. J. Pharmacol. 402, 95–99 (2000)
A. Ceriello, Diabetes Care. 26, 1589–1596 (2003)
J. Xu, Z. Xie, R. Reece, D. Pimental, M.H. Zou, Arterioscler. Thromb. Vasc. Biol. 26, 2688–2695 (2006)
J. Sun, L.J. Druhan, J.L. Zweier, Arch. Biochem. Biophys. 471, 126–133 (2008)
T. Thum, D. Fraccarollo, M. Schultheiss, S. Froese, P. Galuppo et al., Diabetes 56, 666–674 (2007)
S. Blakely, A. Herbert, M. Collins, M. Jenkins, G. Mitchell et al., J. Nutr. 133, 2838–2844 (2003)
P. Faure, Clin. Chem. Lab. Med. 41, 995–998 (2003)
J.L. Evans, Indian J. Med. Res. 125, 355–372 (2007)
J. Garrow, W. James, A. Ralph, Human Nutrition and Dietetics (Churchill Livingstone, New York, NY, 2002)
C. Douillet, A. Tabib, M. Bost, M. Accominotti, F. Borson-Chazot, M. Ciavatti, Proc. Soc. Exp. Biol. Med. 211, 323–331 (1996)
M. Brownlee, Nature 414, 813–820 (2001)
S. Yim, A. Malhotra, A. Veves, Curr. Diab Rep. 7, 8–13 (2007)
G. Lastra, C. Manrique, Antioxid. Redox Signal. 9, 943–954 (2007)
A.L. Tan, J.M. Forbes, M.E. Cooper, Semin. Nephrol. 27, 130–143 (2007)
H.B. Lee, J.Y. Seo, M.R. Yu, S.T. Uh, H. Ha, Kidney Int. 72, S67–S70 (2007)
D. Behne, A. Kyriakopoulos, Annu. Rev. Nutr. 21, 453–473 (2001)
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.
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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
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DOI: https://doi.org/10.1007/s12020-008-9121-7