Skip to main content
SpringerLink
Log in

Diosgenin attenuates vascular calcification in chronic renal failure rats

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Vascular calcification due to elevated phosphate levels is the major contributor of cardiovascular dysfunction. The oxidative stress and gene expression events modulate the transdifferentiation of vascular smooth muscle cells into osteogenic phenotype. This present study intends to evaluate the dose-dependent effect of diosgenin, an antioxidant on high phosphate induced vascular calcification in adenine-induced chronic renal failure rats. High phosphate environment causes elevated calcium accumulation with related histological changes and alkaline phosphatase activity in aorta. Further it downregulates the activity of enzymatic antioxidants and elevates the level of lipid peroxidative markers. Moreover, the renal failure leads to reduced nitric oxide production. But, treatment with diosgenin at a dose of 10, 20, and 40 mg/kg given via oral gavages causes reversion of all the above events in a dose-dependent manner. The highest dose has shown more potential activity than other two doses, which has the ability to protect the alteration of liver markers and red blood cell antioxidant system without any adverse effects and it does not alter the kidney associated changes too. Finally, the Fourier transform infrared spectroscopy study strongly supports its ability to protect the macromolecules from oxidative stress. All the above evidences show that diosgenin has overall benefits against renal failure-induced vascular calcification-associated oxidative stress.

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

Access this article

Log in via an institution

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

Similar content being viewed by others

References

  1. Anderson HC (1983) Calcific diseases. A concept. Arch Pathol Lab Med 107:341–348

    PubMed  CAS  Google Scholar 

  2. Bostrom K, Watson KE, Horn S, Wortham C, Herman IM, Demer LL (1993) Bone morphogenetic protein expression in human atherosclerotic lesions. J Clin Investig 91:1800–1809

    Article  PubMed  CAS  Google Scholar 

  3. Mohler ER, Gannon F, Reynolds C, Zimmerman R, Keane MG, Kaplan FS (2001) Bone formation and inflammation in cardiac valves. Circulation 103:1522–1528

    Article  PubMed  Google Scholar 

  4. Shanahan CM, Cary NR, Salisbury JR, Proudfoot D, Weiss-berg PL, Edmonds ME (1999) Medial localization of mineralization-regulating proteins in association with Monckeberg’s sclerosis: evidence for smooth muscle cell-mediated vascular calcification. Circulation 100:2168–2176

    Article  PubMed  CAS  Google Scholar 

  5. Tyson KL, Reynolds JL, McNair R, Zhang Q, Weissberg PL, Shanahan CM (2003) Osteo/chondrocytic transcription factors and their target genes exhibit distinct patterns of expression in human arterial calcification. Arterioscler Thromb Vasc Biol 23:489–494

    Article  PubMed  CAS  Google Scholar 

  6. Davies JD, Carpenter KL, Challis IR, Figg NL, McNair R, Proudfoot D, Weissberg PL, Shanahan CM (2005) Adipocytic differentiation and liver X receptor pathways regulate the accumulation of triacyl-glycerols in human vascular smooth muscle cells. J Biol Chem 280:3911–3919

    Article  PubMed  CAS  Google Scholar 

  7. Tintut Y, Alfonso Z, Saini T, Radcliff K, Watson K, Bostrom K, Demer LL (2003) Multilineage potential of cells from the artery wall. Circulation 108:2505–2510

    Article  PubMed  Google Scholar 

  8. Massy ZA, Mazière C, Kamel S, Brazier M, Choukroun G, Tribouilloy C, Slama M, Andrejak M, Mazière JC (2005) Impact of inflammation and oxidative stress on vascular calcifications in chronic kidney disease. Pediatr Nephrol 20:380–382

    Article  PubMed  CAS  Google Scholar 

  9. Sherki YG, Rosenbaum Z, Melamed E, Offen D (2006) Antioxidant therapy in acute central nervous system injury: current state. Pharmacol Rev 54:271–284

    Article  Google Scholar 

  10. Johnson RC, Leopold JA, Loscalzo J (2006) Vascular calcification: pathobiological mechanisms and clinical implications. Circ Res 99:1044–1059

    Article  PubMed  CAS  Google Scholar 

  11. Yamada S, Taniguchi M, Tokumoto M, Toyonaga J, Fujisaki K, Suehiro T, Noguchi H, Iida M, Tsuruya K, Kitazono T (2012) The antioxidant tempol ameliorates arterial medial calcification in uremic rats: important role of oxidative stress in the pathogenesis of vascular calcification in chronic kidney disease. J Bone Miner Res 27:474–485

    Article  PubMed  CAS  Google Scholar 

  12. Shishodia S, Aggarwal BB (2005) Diosgenin inhibits osteoclastogenesis, invasion, and proliferation through the downregulation of Akt, IκB kinase activation and NF-κB-regulated gene expression. Oncogene 25:1463–1473

    Article  Google Scholar 

  13. Adlercreutz H, Markkanen H, Watanabe S (1993) Plasma concentrations of phyto-oestrogens in Japanese men. Lancet 342:1209–1210

    Article  PubMed  CAS  Google Scholar 

  14. Hertog MG, Kromhout D, Aravanis C, Blackburn H, Buzina R, Fidanza F, Giampaoli S, Jansen A, Menotti A, Nedeljkovic S (1995) Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study. Arch Intern Med 155:381–386

    Article  PubMed  CAS  Google Scholar 

  15. Figtree GA, Griffiths H, Lu YQ, Webb CM, MacLeod K, Collins P (2000) Plant-derived estrogens relax coronary arteries in vitro by a calcium antagonistic mechanism. J Am Coll Cardiol 35:1977–1985

    Article  PubMed  CAS  Google Scholar 

  16. Au AL, Kwok CC, Lee AT, Kwan YW, Lee MM, Zhang RZ, Ngai SM, Lee SM, He GW, Fung KP (2004) Activation of iberiotoxin-sensitive, Ca2-activated Kchan-nels of porcine isolated left anterior descending coronary artery by diosgenin. Eur J Pharmacol 502:123–133

    Article  PubMed  CAS  Google Scholar 

  17. Choi KW, Park HJ, Jung DH, Kim TW, Park YM, Kim BO, Sohn EH, Moon EY, Um SH, Rhee DK, Pyo S (2010) Inhibition of TNF-α-induced adhesion molecule expression by diosgenin in mouse vascular smooth muscle cells via downregulation of the MAPK, Akt and NF-κB signaling pathways. Vasc Pharmacol 53:273–280

    Article  CAS  Google Scholar 

  18. Pari L, Monisha P, Jalaludeen AM (2012) Beneficial role of diosgenin on oxidative stress in aorta of streptozotocin induced diabetic rats. Eur J Pharmacol 691:143–150

    Article  PubMed  CAS  Google Scholar 

  19. Sutliff RL, Walp ER, El-Ali AM, Elkhatib S, Lomashvili KA, O’Neill WC (2011) Effect of medial calcification on vascular function in uremia. Am J Physiol Renal Physiol 301:F78–F83

    Article  PubMed  CAS  Google Scholar 

  20. Zhou Y-B, Jin S-J, Cai Y, Teng X, Chen L, Tang C-S, Qi Y-F (2009) Lanthanum acetate inhibits vascular calcification induced by vitamin D3 plus nicotine in rats. Exp Biol Med 234:908–917

    Article  CAS  Google Scholar 

  21. Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids. Anal Biochem 126:131–138

    Article  PubMed  CAS  Google Scholar 

  22. Kakkar P, Das B, Viswanathan PN (1984) A modified spectrophotometric assay of superoxide dismutase. Ind J Biochem Biophys 21:130–132

    CAS  Google Scholar 

  23. Sinha AK (1972) Colorimetric assay of catalase. Anal Biochem 47:389–394

    Article  PubMed  CAS  Google Scholar 

  24. Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG (1973) Selenium: biochemical role as a component of glutathione peroxidise. Science 179:588–590

    Article  PubMed  CAS  Google Scholar 

  25. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with Folin phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  26. Niehaus WG, Samuelson B (1968) Formation of malondialdehyde from phospholipid arachidonate during microsomal lipid peroxidation. Eur J Biochem 6:126–130

    Article  PubMed  CAS  Google Scholar 

  27. Jiang ZY, Hunt JV, Wolff SP (1992) Ferrous ion oxidation in the presence of xylenol orange for detection of lipid hydroperoxide in low density lipoprotein. Anal Biochem 202:384–389

    Article  PubMed  CAS  Google Scholar 

  28. Fawcett JK, Scott JE (1960) A rapid and precise method for the determination of urea. J Clin Pathol 13:156–159

    Article  PubMed  CAS  Google Scholar 

  29. Caraway WT (1955) Determination of uric acid in serum by carbonate method. Am J Clin Pathol 25:840–845

    PubMed  CAS  Google Scholar 

  30. Jaffe M (1886) Concerning the precipitate produced in normal urine by picric acid and a new reaction of creatinine. Z Physiol Chem 10:391–400

    Google Scholar 

  31. Rosalki SB, Rau D (1972) Serum-glutamyl transpeptidase activity in alcoholism. Clin Chim Acta 39:41–47

    Article  PubMed  CAS  Google Scholar 

  32. Sivakumar S, Sivasubramanian J, Raja B (2012) Aluminium induced structural, metabolic alterations and protective effects of desferrioxamine in the brain tissue of mice: An FTIR study. Spectrochimica Acta Part A 99:252–258. doi:10.1016/j.saa.2012.09.036

    Article  CAS  Google Scholar 

  33. Saravanakumar M, Manivannan J, Sivasubramanian J, Silambarasan T, Balamurugan E, Raja B (2012) Molecular metabolic fingerprinting approach to investigate the effects of borneol on metabolic alterations in the liver of nitric oxide deficient hypertensive rats. Mol Cell Biochem 362:203–209

    Article  PubMed  CAS  Google Scholar 

  34. Cakmak G, Togan I, Severcan F (2006) 17-Estradiol induced com-positional, structural and functional changes in rainbow trout liver, revealed by FT-IR spectroscopy: a comparative study with nonyl-phenol. Aquat Toxicol 77:53–63

    Article  PubMed  CAS  Google Scholar 

  35. Kircelli F, Peter ME, Sevinc Ok E, Celenk FG, Yilmaz M, Steppan S, Asci G, Ok E, Passlick-Deetjen J (2012) Magnesium reduces calcification in bovine vascular smooth muscle cells in a dose-dependent manner. Nephrol Dial Transplant 27:514–521

    Article  PubMed  CAS  Google Scholar 

  36. Shan PF, Lu Y, Cui RR, Jiang Y, Yuan LQ, Liao EY (2011) Apelin attenuates the osteoblastic differentiation of vascular smooth muscle cells. PLoS ONE 6(3):e17938. doi:10.1371/journal.pone.0017938

    Article  PubMed  CAS  Google Scholar 

  37. Kapustin A, Galkin A, Furmanik M, Hernandez AD, Shanahan C (2011) Elevated calcium and phosphate impair mitochondrial function in calcifying human vascular smooth muscle cell. Heart 97(24) doi:10.1136/heartjnl-2011-301156.19

  38. Kim H, Kim HJ, Lee K, Kim JM, Kim HS, Kim JR, Ha CM, Choi YK, Lee SJ, Kim JY, Harris RA, Jeong D, Lee IK (2012) α-Lipoic acid attenuates vascular calcification via reversal of mitochondrial function and restoration of Gas6/Axl/Akt survival pathway. J Cell Mol Med 16:273–286

    Article  PubMed  CAS  Google Scholar 

  39. Frank L, Massaro D (1980) Oxygen toxicity. Am J Med 69:117–126

    Article  PubMed  CAS  Google Scholar 

  40. Byon CH, Javed A, Dai Q, Kappes JC, Clemens TL, Darley-Usmar VM, McDonald JM, Chen Y (2008) Oxidative stress induces vascular calcification through modulation of the osteogenic transcription factor Runx2 by AKT signaling. J Biol Chem 283:15319–15327

    Article  PubMed  CAS  Google Scholar 

  41. Jayachandran KS, Vasanthi HR, Rajamanickam GV (2009) Antilipoperoxidative and membrane stabilizing effect of diosgenin, in experimentally induced myocardial infarction. Mol Cell Biochem 327:203–210

    Article  PubMed  CAS  Google Scholar 

  42. Van TV, Watari E, Taketani Y, Kitamura T, Shiota A, Tanaka T, Tanimura A, Harada N, Nakaya Y, Yamamoto H, Miyamoto K, Takeda E (2012) Dietary phosphate restriction ameliorates endothelial dysfunction in adenine-induced kidney disease rats. J Clin Biochem Nutr 51:27–32

    Article  PubMed  CAS  Google Scholar 

  43. Severcan F (1997) Vitamin E decreases the order of the phospholipids model membranes in the gel phase: an FT-IR study. Biosci Rep 17:231–235

    Article  PubMed  CAS  Google Scholar 

  44. Rice-Evans CA, Diplock AT, Symos MCR (1991) Technique in free radical research. Elsevier, New York, pp 207–218

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, 608 002, Tamilnadu, India

    Jeganathan Manivannan, Pandian Arunagiri, Boobalan Raja & Elumalai Balamurugan

  2. Faculty of Marine Sciences, Annamalai University, Parangipettai, 608 502, Tamilnadu, India

    T. R. Barathkumar

  3. Department of Physics, Faculty of Science, Annamalai University, Annamalainagar, 608 002, Tamilnadu, India

    Jeganathan Sivasubramanian

Authors
  1. Jeganathan Manivannan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. R. Barathkumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jeganathan Sivasubramanian
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pandian Arunagiri
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Boobalan Raja
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Elumalai Balamurugan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elumalai Balamurugan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Manivannan, J., Barathkumar, T.R., Sivasubramanian, J. et al. Diosgenin attenuates vascular calcification in chronic renal failure rats. Mol Cell Biochem 378, 9–18 (2013). https://doi.org/10.1007/s11010-013-1588-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-013-1588-8

Keywords

Search

Navigation