, 24:943 | Cite as

Influence of vanadium supplementation on oxidative stress factors in the muscle of STZ-diabetic rats

  • Ozlem Kurt
  • Tugba Yilmaz Ozden
  • Nurten Ozsoy
  • Sevim Tunali
  • Ayse Can
  • Nuriye Akev
  • Refiye Yanardag


In recent years, the role of free radical damage consequent to oxidative stress is widely discussed in diabetic complications. In this aspect, the protection of cell integrity by trace elements is a topic to be investigated. Vanadium is a trace element believed to be important for normal cell function and development. The aim of the present study was to investigate the effect of vanadyl sulfate supplementation on the antioxidant system in the muscle tissue of diabetic rats. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ, 65 mg/kg body weight) to male Swiss albino rats. The rats were randomly divided into 4 groups: Group I, control; Group II, vanadyl sulfate control; Group III, STZ-diabetic untreated; Group IV, STZ-diabetic treated with vanadyl sulfate. Vanadyl sulfate (100 mg/kg) was given daily by gavage for 60 days. At the last day of the experiment, rats were killed, muscle tissues were taken, homogenized in cold saline to make a 10% (w/v) homogenate. Body weights and blood glucose levels were estimated at 0, 30 and 60th days. Antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), as well as carbonic anhydrase (CA), myeloperoxidase (MPO) activities and protein carbonyl content (PCC) were determined in muscle tissue. Vanadyl sulfate administration improved the loss in body weight due to STZ-induced diabetes and decreased the rise in blood glucose levels. It was shown that vanadium supplementation to diabetic rats significantly decrease serum antioxidant enzyme levels, which were significantly raised by diabetes in muscle tissue showing that this trace element could be used as preventive for diabetic complications.


Vanadium Antioxidant enzymes Muscle Diabetes mellitus Streptozotocin 


  1. Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126PubMedCrossRefGoogle Scholar
  2. Akgün-Dar K, Bolkent S, Yanardag R, Tunali S (2007) Vanadyl sulfate protects against streptozotocin-induced morphological and biochemical changes in rat aorta. Cell Biochem Funct 25:603–609PubMedCrossRefGoogle Scholar
  3. Badmaev V, Prakash S, Majeed M (1999) Vanadium: a review of its potential role in the fight against diabetes. J Altern Complement Med 5:273–291PubMedCrossRefGoogle Scholar
  4. Bakhtiar R, Ochiai E-I (1999) Pharmacological applications of inorganic complexes. Gen Pharmacol 32:525–540PubMedCrossRefGoogle Scholar
  5. Baynes JW (1991) Role of oxidative stress in development of complications in diabetes. Diabetes 40:405–412PubMedCrossRefGoogle Scholar
  6. Bendayan M, Gingras D (1989) Effect of vanadate administration on blood glucose and insulin levels as well as on the exocrine pancreatic function in streptozotocin-diabetic rats. Diabetologia 32:561–567PubMedCrossRefGoogle Scholar
  7. Berlett BS, Stadman ER (1997) Protein oxidation in aging, disease and oxidative stress. J Biol Chem 272:20313–20316PubMedCrossRefGoogle Scholar
  8. Boden G, Chen X, Ruiz J, van Rossum GDV, Turco S (1996) Effects of vanadyl sulfate on carbohydrate and lipid metabolism in patients with non-insulin-dependent diabetes mellitus. Metabolism 45:1130–1135PubMedCrossRefGoogle Scholar
  9. Bolkent S, Bolkent S, Yanardag R, Tunali S (2005) Protective effect of vanadyl sulfate on the pancreas of streptozotocin-induced diabetic rats. Diabetes Res Clin Pract 70:103–109PubMedCrossRefGoogle Scholar
  10. Cantley LC Jr, Josephson L, Warner R, Yanagisawa M, Lechene C, Guidotti G (1977) Vanadate is a potent (Na, K)-ATPase inhibitor found in ATP derived from muscle. J Biol Chem 252:7421–7423PubMedGoogle Scholar
  11. Carlberg I, Mannervik B (1977) Purification by affinity chromatography of yeast glutathione reductase, the enzyme responsible for the NADPH-dependent reduction of the mixed disulfide of coenzyme A and glutathione. Biochim Biophys Acta 484:268–274PubMedGoogle Scholar
  12. Chakraborty T, Chatterjee A, Rana A, Dhachinamoorthi D, Kumar PA, Chatterjee M (2007) Carcinogen-induced early molecular events and its implication in the initiation of chemical hepatocarcinogenesis in rats: chemopreventive role of vanadium on this process. Biochim Biophys Acta 1772:48–59PubMedGoogle Scholar
  13. Clark AS, Fagan JM, Mitch WE (1985) Selectivity of the insulin-like actions of vanadate on glucose and protein metabolism in skeletal muscle. Biochem J 232:273–276PubMedGoogle Scholar
  14. Dai S, Thompson KH, McNeill JH (1994) One-year treatment of streptozotocin-induced diabetic rats with vanadyl sulphate. Pharmacol Toxicol 74:101–109PubMedCrossRefGoogle Scholar
  15. Gumieniczek A, Hopkała H, Wójtowicz Z, Nikołajuk J (2002) Changes in antioxidant status of heart muscle tissue in experimental diabetes in rabbits. Acta Biochim Pol 49:529–535PubMedGoogle Scholar
  16. Habig WH, Jakoby WB (1981) Assays for differentiation of glutathione-S-transferases. Methods Enzymol 77:398–405PubMedCrossRefGoogle Scholar
  17. Heyliger CE, Tahiliani AG, McNeill JH (1985) Effect of vanadate on elevated blood glucose and depressed cardiac performance of diabetic rats. Science 227:1474–1477PubMedCrossRefGoogle Scholar
  18. Hillegass LM, Griswold DE, Brickson B, Albrightson-Winslow C (1990) Assessment of myeloperoxidase activity in whole rat kidney. J Pharmacol Methods 24:285–295PubMedCrossRefGoogle Scholar
  19. Hopfner RL, McNeill JR, Gopalakrishnan V (1998) Vanadate treatment normalizes exaggerated vascular smooth muscle responses in the obese Zucker rat. Eur J Pharmacol 357:61–65PubMedCrossRefGoogle Scholar
  20. Jandhyala BS, Hom GJ (1983) Minireview: physiological and pharmacological properties of vanadium. Life Sci 33:1325–1340PubMedCrossRefGoogle Scholar
  21. Junod A, Lambert AE, Stauffacher W, Renold AE (1969) Diabetogenic action of streptozotocin: relationship of dose to metabolic response. J Clin Invest 48:2129–2139PubMedCrossRefGoogle Scholar
  22. Koyuturk M, Tunali S, Bolkent S, Yanardag R (2005) Effects of vanadyl sulfate on liver of streptozotocin-induced diabetic rats. Biol Trace Elem Res 104:233–247PubMedCrossRefGoogle Scholar
  23. Lapenna D, Ciofani G, Bruno C, Pierdomenico SD, Giuliani L, Giamberardino MA, Cuccurullo F (2002) Vanadyl as a catalyst of human lipoprotein oxidation. Biochem Pharmacol 63:375–380PubMedCrossRefGoogle Scholar
  24. Larbi EB (1998) Drug-induced rhabdomyolysis. Ann Saudi Med 18:525–530PubMedGoogle Scholar
  25. Lawrence RA, Burk RF (1976) Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun 71:952–958PubMedCrossRefGoogle Scholar
  26. Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz A-G, Ahn B-W, Shaltiel S, Stadtman ER (1990) Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 186:464–478PubMedCrossRefGoogle Scholar
  27. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  28. Maruyama Y, Lindholm B, Stenvinkel P (2004) Inflammation and oxidative stress in ESRD the role of myeloperoxidase. J Nephrol 17(Suppl. 8):72–76Google Scholar
  29. Marzban L, McNeill JH (2003) Insulin-like actions of vanadium: potential as a therapeutic agent. J Trace Element Exp Med 16:253–267CrossRefGoogle Scholar
  30. Matkovics B, Varga SI, Szabó L, Witas H (1982) The effect of diabetes on the activities of the peroxide metabolism enzymes. Horm Metab Res 14:77–79PubMedCrossRefGoogle Scholar
  31. Mohammad A, Sharma V, McNeill JH (2002) Vanadium increases GLUT4 in diabetic rat skeletal muscle. Mol Cell Biochem 233:139–143PubMedCrossRefGoogle Scholar
  32. Mongold JJ, Cros GH, Vian L, Tep A, Ramanadham S, Siou G, Diaz J, McNeill JH, Serrano JJ (1990) Toxicological aspects of vanadyl sulphate on diabetic rats: effects on vanadium levels and pancreatic B-cell morphology. Pharmacol Toxicol 67:192–198PubMedCrossRefGoogle Scholar
  33. Mylroie AA, Collins H, Umbles C, Kyle J (1986) Erythrocyte superoxide dismutase activity and other parameters of copper status in rats ingesting lead acetate. Toxicol Appl Pharmacol 82:512–520PubMedCrossRefGoogle Scholar
  34. Pepato MT, Khalil NM, Giocondo MP, Brunetti IL (2008) Vanadium and its complexes: the renewed interest in its biochemistry. Lat Am J Pharm 27:468–476Google Scholar
  35. Poucheret P, Verma S, Grynpas MD, McNeill JH (1998) Vanadium and diabetes. Mol Cell Biochem 188:73–80PubMedCrossRefGoogle Scholar
  36. Räisänen SR, Lehenkari P, Tasanen M, Rahkila P, Härkönen PL, Väänänen HK (1999) Carbonic anhydrase III protects cells from hydrogen peroxide-induced apoptosis. FASEB J 13:513–522PubMedGoogle Scholar
  37. Ravi K, Ramachandran B, Subramanian S (2004) Protective effect of Eugenia jambolana seed kernel on tissue antioxidants in streptozotocin-induced diabetic rats. Biol Pharm Bull 27:1212–1217PubMedCrossRefGoogle Scholar
  38. Rehder D (2003) Biological and medicinal aspects of vanadium. Inorg Chem Commun 6:604–617CrossRefGoogle Scholar
  39. Relander A, Raiha CE (1963) Differences between the enzymatic and toluidine methods of blood glucose determination. Scand J Clin Lab Invest 15:221–224CrossRefGoogle Scholar
  40. Reznick AZ, Packer L (1994) Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Methods Enzymol 233:357–363PubMedCrossRefGoogle Scholar
  41. Roman RM, Wendland AE, Polanczyk CA (2007) Myeloperoxidase and coronary arterial disease: from research to clinical practice. Arq Bras Cardiol 91:e11–e18Google Scholar
  42. Sakurai H, Tsuchiya K, Nukatsuka M, Sofue M, Kawada J (1990) Insulin-like effect of vanadyl ion on streptozotocin-induced diabetic rats. J Endocrinol 126:451–459PubMedCrossRefGoogle Scholar
  43. Semiz S, Mc Neill JH (2002) Oral treatment with vanadium of Zucker fatty rats activates muscle glycogen synthesis and insulin-stimulated protein phosphatase-1 activity. Mol Cell Biochem 236:123–131PubMedCrossRefGoogle Scholar
  44. Singbartl K, Green SA, Ley K (2000) Blocking P-selectin protects from ischemia/reperfusion-induced acute renal failure. FASEB J 14:48–54PubMedGoogle Scholar
  45. Singh N, Kamath V, Narasimhamurthy K, Rajini PS (2008) Protective effect of potato peel extract against carbon tetrachloride-induced liver injury in rats. Environ Toxicol Pharmacol 26:241–246PubMedCrossRefGoogle Scholar
  46. Srivastava AK (2000) Anti-diabetic and toxic effects of vanadium compounds. Mol Cell Biochem 206:177–182PubMedCrossRefGoogle Scholar
  47. Stohs SJ, Bagchi D (1995) Oxidative mechanisms in the toxicity of metal ions. Free Radic Biol Med 18:321–336PubMedCrossRefGoogle Scholar
  48. Thompson KH (1999) Vanadium and diabetes. Biofactors 10:43–51PubMedCrossRefGoogle Scholar
  49. Thompson KH, Orvig C (2001) Coordination chemistry of vanadium in metallopharmaceutical candidate compounds. Coord Chem Rev 219–221:1033–1053CrossRefGoogle Scholar
  50. Thompson KH, McNeill JH, Orvig C (1999) Vanadium compounds as insulin mimics. Chem Rev 99:2561–2571PubMedCrossRefGoogle Scholar
  51. Tsiani E, Fantus IG (1997) Vanadium compounds biological actions and potential as pharmacological agents. Trends Endocrinol Metab 8:51–58PubMedCrossRefGoogle Scholar
  52. Tunali S, Yanardag R (2006) Effect of vanadyl sulfate on the status of lipid parameters and on stomach and spleen tissues of streptozotocin-induced diabetic rats. Pharmacol Res 53:271–277PubMedCrossRefGoogle Scholar
  53. Verpoorte JA, Mehta S, Edsall JT (1967) Esterase activities of human carbonic anhydrases B and C. J Biol Chem 242:4221–4229PubMedGoogle Scholar
  54. Wang G, Zhang L, Li Q (2006) Genetic polymorphisms of GSTT1, GSTM1, and NQO1 genes and diabetes mellitus risk in Chinese population. Biochem Biophys Res Commun 341:310–313PubMedCrossRefGoogle Scholar
  55. Wronska-Nofer T, Wisniewska-Knypl J, Dziubaltowska E, Wysznska K (1999) Prooxidative and genotoxic effect of transition metals (cadmium, nickel, chromium, and vanadium) in mice. Trace Elem Electrolyte 16:87–92Google Scholar
  56. Yanardag R, Tunali S (2006) Vanadyl sulfate administration protects the streptozotocin-induced oxidative damage to brain tissue in rats. Mol Cell Biochem 286:153–159PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Ozlem Kurt
    • 1
  • Tugba Yilmaz Ozden
    • 1
  • Nurten Ozsoy
    • 1
  • Sevim Tunali
    • 2
  • Ayse Can
    • 1
  • Nuriye Akev
    • 1
  • Refiye Yanardag
    • 2
  1. 1.Department of BiochemistryFaculty of Pharmacy, Istanbul UniversityBeyazit-IstanbulTurkey
  2. 2.Department of ChemistryFaculty of Engineering, Istanbul UniversityAvcilar-IstanbulTurkey

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