Pediatric Nephrology

, 26:1809 | Cite as

RETRACTED ARTICLE: Soy protein prevents renal damage in a fructose-induced model of metabolic syndrome via inhibition of NF-kB in male rats

  • Nallasamy Palanisamy
  • Carani Venkataraman Anuradha
Original Article

Abstract

The study determines the effect of soy protein on inflammatory status and expression of nuclear factor-kappa B (NF-κB P65) and receptor for advanced glycation end products (RAGE) in a metabolic syndrome (MS) model. MS was induced in adult male rats by feeding them a high fructose diet (60 g/100 g diet). The rats were randomised into six groups by feeding one of the following semi-synthetic diets for 60 days: corn starch (60%) and casein (20%; CCD), fructose (60%) and casein (20%; FCD), fructose (60%) and soy protein (20%; FSD) or corn starch (60%) and soy protein (20%; CSD). The expression of NF-κB P65, transforming growth factor-β1 (TGF-β1) and RAGE, histochemical localization of α-smooth muscle actin (α-SMA), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) assays, collagen deposition and ultrastructural analysis were performed. FCD rats displayed inflammatory changes and increased expression of growth factors and nuclear factors. FSD rats showed reduction in inflammation, fibrogenesis, collagen deposition, NF-κB activation and mitigated the ultrastructural changes. Soy protein prevents inflammation and early nephropathic changes in the MS model secondary to the attenuation of NF-κB activation.

Keywords

Kidney Soy protein Fructose Insulin resistance Collagen 

References

  1. 1.
    Elliott SS, Keim NL, Stern JS, Teff K, Havel PJ (2002) Fructose, weight gain, and the insulin resistance syndrome. Am J Clin Nutr 76:911–922PubMedGoogle Scholar
  2. 2.
    Sánchez-Lozada LG, Tapia E, Jiménez A, Bautista P, Cristóbal M, Nepomuceno T, Soto V, Avila-Casado C, Nakagawa T, Johnson RJ, Herrera-Acosta J, Franco M (2007) Fructose-induced metabolic syndrome is associated with glomerular hypertension and renal microvascular damage in rats. Am J Physiol Ren Physiol 292:F423–F429CrossRefGoogle Scholar
  3. 3.
    Zhou G, Li C, Cai L (2004) Advanced glycation end-products induce connective tissue growth factor-mediated renal fibrosis predominantly through transforming growth factor beta-independent pathway. Am J Pathol 165:2033–2043PubMedCrossRefGoogle Scholar
  4. 4.
    Navarro-González JF, Mora-Fernández C (2008) The role of inflammatory cytokines in diabetic nephropathy. J Am Soc Nephrol 19:433–442PubMedCrossRefGoogle Scholar
  5. 5.
    Lazar MA (2006) The humoral side of insulin resistance. Nat Med 12:43–54PubMedCrossRefGoogle Scholar
  6. 6.
    Dandona P, Aljada A, Bandyopadhyay A (2004) Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol 25:4–7PubMedCrossRefGoogle Scholar
  7. 7.
    Tan AL, Forbes JM, Cooper ME (2007) AGE, RAGE, and ROS in diabetic nephropathy. Semin Nephrol 27:130–143PubMedCrossRefGoogle Scholar
  8. 8.
    Bierhaus A, Humpert PM, Morcos M, Wendt T, Chavakis T, Arnold B, Stern DM, Nawroth PP (2005) Understanding RAGE, the receptor for advanced glycation end products. J Mol Med 83:876–886PubMedCrossRefGoogle Scholar
  9. 9.
    Moynagh PN (2005) The NF-κB pathway. J Cell Sci 118:4389–4392CrossRefGoogle Scholar
  10. 10.
    Tan HW, Xing SS, Bi XP, Li L, Gong HP, Zhong M, Zhang Y, Zhang W (2008) Felodipine attenuates vascular inflammation in a fructose-induced rat model of metabolic syndrome via the inhibition of NF-kappa B activation. Acta Pharmacol Sin 29:1051–1059PubMedCrossRefGoogle Scholar
  11. 11.
    Azadbakht L, Shakerhosseini R, Atabak S, Jamshidian M, Mehrabi Y, Esmaill-Zadeh A (2003) Beneficiary effect of dietary soy protein on lowering plasma levels of lipid and improving kidney function in type II diabetes with nephropathy. Eur J Clin Nutr 57:1292–1294PubMedCrossRefGoogle Scholar
  12. 12.
    Tovar AR, Murguía F, Cruz C, Hernández-Pando R, Aguilar-Salinas CA, Pedraza-Chaverri J, Correa-Rotter R, Torres N (2002) A soy protein diet alters hepatic lipid metabolism gene expression and reduces serum lipids and renal fibrogenic cytokines in rats with chronic nephrotic syndrome. J Nutr 132:2562–2569PubMedGoogle Scholar
  13. 13.
    Lavigne C, Marette A, Jacques H (2000) Cod and soy proteins compared with casein improve glucose tolerance and insulin sensitivity in rats. Am J Physiol Endocrinol Metab 278:491–500Google Scholar
  14. 14.
    Palanisamy N, Viswanathan P, Ravichandran MK, Anuradha CV (2010) Renoprotective and blood pressure lowering effect of dietary soy protein via protein kinase C-β II inhibition in a rat model of metabolic syndrome. Can J Physiol Pharmacol 88:28–37PubMedCrossRefGoogle Scholar
  15. 15.
    Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419PubMedCrossRefGoogle Scholar
  16. 16.
    Woessner JF (1961) The determination of hydroxy proline in tissue and protein samples containing small portions of this amino acid. Arch Biochem Biophys 93:440–447PubMedCrossRefGoogle Scholar
  17. 17.
    Paz MA, Lent RW, Faris B, Frazblan C, Blumfeld OO, Gallop PM (1969) Aldehydes in native and denatured calfskin procollagen. Biochem Biophys Res Com 34:221–229PubMedCrossRefGoogle Scholar
  18. 18.
    Rao P, Pattabiraman TN (1990) Reevaluation of the phenol sulphuric acid reaction for the estimation of hexoses and pentoses. Anal Biochem 181:18–22CrossRefGoogle Scholar
  19. 19.
    Niehaus WG, Samuelson B (1986) Formation of MDA from phospholipid arachidonate during microsomal lipid peroxidation. Eur J Biochem 6:126–130CrossRefGoogle Scholar
  20. 20.
    Miller EJ, Rhodes RK (1982) Preparation and characterization of different types of collagen. Meth Enzymol 82:33–64PubMedCrossRefGoogle Scholar
  21. 21.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin’s-Phenol reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  22. 22.
    Palanisamy N, Viswanathan P, Anuradha CV (2008) Effect of genistein, a soy isoflavone, on whole body insulin sensitivity and renal damage induced by a high-fructose diet. Ren Fail 30:645–654PubMedCrossRefGoogle Scholar
  23. 23.
    Levi B, Werman MJ (1998) Long-term fructose consumption accelerates glycation and several age-related variables. J Nutr 128:1442–1449PubMedGoogle Scholar
  24. 24.
    Vasdev S, Ford CA, Longerich L, Gadag V, Wadhawan S (1998) Role of aldehydes in fructose-induced hypertension. Mol Cell Biochem 181:1–9PubMedCrossRefGoogle Scholar
  25. 25.
    Alexandraki K, Piperi C, Kalofoutis C, Singh J, Alaveras A, Kalofoutis A (2006) The inflammatory process in type 2 diabetes. The role of cytokines. Ann N Y Acad Sci 1084:89–117PubMedCrossRefGoogle Scholar
  26. 26.
    Chang JW, Kim CS, Kim SB, Park SK, Park JS, Lee SK (2006) Proinflammatory cytokine-induced NF-kappa B activation in human mesangial cells is mediated through intracellular calcium but not ROS: effects of silymarin. Nephron Exp Nephrol 103:156–165CrossRefGoogle Scholar
  27. 27.
    Ortiz A, Bustos C, Alonso J, Alcázar R, López-Armada MJ, Plaza JJ, González E, Egido J (1995) Involvement of tumor necrosis factor-alpha in the pathogenesis of experimental and human glomerulonephritis. Adv Nephrol Necker Hosp 24:53–77PubMedGoogle Scholar
  28. 28.
    Navarro JF, Milena FJ, Mora C, Leon C, Garcıa J (2006) Renal pro-inflammatory cytokine gene expression in diabetic nephropathy: effect of angiotensin-converting enzyme inhibition and pentoxifylline administration. Am J Nephrol 26:562–570PubMedCrossRefGoogle Scholar
  29. 29.
    Dalla Vestra M, Mussap M, Gallina P, Bruseghin M, Cernigoi AM, Saller A, Plebani M, Fioretto P (2005) Acute-phase markers of inflammation and glomerular structure in patients with type 2 diabetes. J Am Soc Nephrol 16:S78–S82PubMedCrossRefGoogle Scholar
  30. 30.
    Coleman DL, Ruef C (1992) Interleukin-6: an autocrine regulator of mesangial cell growth. Kidney Int 41:604–606PubMedCrossRefGoogle Scholar
  31. 31.
    Prud’homme GJ (2007) Pathobiology of transforming growth factor (beta) in cancer, fibrosis and immunologic disease, and therapeutic considerations. Lab Invest 87:1077–1091PubMedCrossRefGoogle Scholar
  32. 32.
    Sharma K, Ziyadeh FN (1995) Hyperglycemia and diabetic kidney disease: the case for transforming growth factor-β1 as a key mediator. Diabetes 4:1139–1146CrossRefGoogle Scholar
  33. 33.
    Wang W, Koka V, Lan HY (2005) Transforming growth factor-(beta) and Smad signalling in kidney diseases. Nephrol 10:48–56CrossRefGoogle Scholar
  34. 34.
    Trujillo J, Cruz C, Tovar A, Vaidya V, Zambrano E, Bonventre JV, Gamba G, Torres N, Bobadilla NA (2008) Renoprotective mechanisms of soy protein intake in the obese Zucker rat. Am J Physiol Ren Physiol 295:F1574–F1582CrossRefGoogle Scholar
  35. 35.
    Pat B, Hughson MB, Nicol J, Hoy WE, Gobe GC (2007) A comparison of pathomolecular markers of fibrosis and morphology in kidney from autopsies of African Americans and whites. Virchows Arch 450:41–50PubMedCrossRefGoogle Scholar
  36. 36.
    Ng YY, Huang TP, Yang WC, Chen ZP, Yang AH, Mu W (1998) Tubular epithelial-myofibroblast transdifferentiation in progressive tubulointerstitial fibrosis in 5/6 nephrectomized rats. Kidney Int 54:864–876PubMedCrossRefGoogle Scholar
  37. 37.
    Smoyer WE, Mundel P (1998) Regulation of podocyte structure during the development of nephrotic syndrome. J Mol Med 76:172–183PubMedCrossRefGoogle Scholar
  38. 38.
    Zhuo J, Ohishi M, Mendelsohn FA (1999) Roles of AT1 and AT2 receptors in the hypertensive Ren-2 gene transgenic rat kidney. Hypertension 33:347–353PubMedCrossRefGoogle Scholar
  39. 39.
    Ijpelaar DH, Schulz A, Koop K, Schlesener M, Bruijn JA, Kerjaschki D, Kreutz R, de Heer E (2008) Glomerular hypertrophy precedes albuminuria and segmental loss of podoplanin in podocytes in Munich-Wistar-Frömter rats. Am J Physiol Ren Physiol 294:758–767CrossRefGoogle Scholar
  40. 40.
    Kerjaschki D (2001) Caught flat-footed: podocyte damage and the molecular bases of focal glomerulosclerosis. J Clin Invest 108:1583–1587PubMedGoogle Scholar
  41. 41.
    Sinha S, Perdomo G, Brown NF, O’Doherty RM (2004) Fatty acid-induced insulin resistance in L6 myotubes is prevented by inhibition of activation and nuclear localization of nuclear factor kappa B. J Biol Chem 279:41294–41301PubMedCrossRefGoogle Scholar
  42. 42.
    Boden G, She P, Mozzoli M, Cheung P, Gumireddy K, Reddy P, Xiang X, Luo Z, Ruderman N (2005) Free fatty acids produce insulin resistance and activate the proinflammatory nuclear factor-kappa B pathway in rat liver. Diabetes 54:3458–3465PubMedCrossRefGoogle Scholar
  43. 43.
    Barma P, Bhattacharya S, Bhattacharya A, Kundu R, Dasgupta S, Biswas A, Bhattacharya S, Roy SS, Bhattacharya S (2009) Lipid induced over expression of NF-kappa B in skeletal muscle cells is linked to insulin resistance. Biochim Biophys Acta 1792:190–200PubMedCrossRefGoogle Scholar
  44. 44.
    Chen L, Zhang J, Zhang Y, Wang Y, Wang B (2008) Improvement of inflammatory responses associated with NF-kB pathway in kidneys from diabetic rat. Inflamm Res 57:199–204PubMedCrossRefGoogle Scholar
  45. 45.
    Tomobe K, Philbrick DJ, Ogborn MR, Takahashi H, Holub BJ (1998) Effect of dietary soy protein and genistein on disease progression in mice with polycystic kidney disease. Am J Kidney Dis 31:55–61PubMedCrossRefGoogle Scholar
  46. 46.
    Maddox DA, Alavi FK, Silbernick EM, Zawada ET (2002) Protective effects of a soy diet in preventing obesity-linked renal disease. Kidney Int 61:96–104PubMedCrossRefGoogle Scholar
  47. 47.
    Gilani GS, Cockell KA, Sepehr E (2005) Effects of antinutritional factors on protein digestibility and amino acid availability in foods. J AOAC Int 88:967–987PubMedGoogle Scholar
  48. 48.
    Vanden Berghe W, Dijsselbloem N, Vermeulen L, Ndlovu N, Boone E, Haegeman G (2006) Attenuation of mitogen- and stress-activated protein kinase-1-driven nuclear factor-kappa B gene expression by soy isoflavones does not require estrogenic activity. Cancer Res 66:4852–4862PubMedCrossRefGoogle Scholar

Copyright information

© IPNA 2011

Authors and Affiliations

  • Nallasamy Palanisamy
    • 1
  • Carani Venkataraman Anuradha
    • 1
  1. 1.Department of Biochemistry and Biotechnology, Faculty of ScienceAnnamalai UniversityAnnamalai NagarIndia

Personalised recommendations