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Molecular and Cellular Biochemistry

, Volume 272, Issue 1–2, pp 157–164 | Cite as

Amelioration of diabetic dyslipidemia by macrocyclic binuclear oxovanadium complex on streptozotocin induced diabetic rats

  • Balasubramanian Ramachandran
  • Sorimuthu Subramanian
Article

Abstract

Diabetic dyslipidemia, the main causative factor for the progression of vascular complications in diabetes, is caused due to hyperglycemia and excess mobilisation of fatty acids. Recently we have reported on a novel macrocyclic binuclear oxovanadium (MBOV) complex synthesized by us with significant hypoglycemic efficacy and without any apparent toxicity on streptozotocin induced diabetic rats. In the present study, streptozotocin induced diabetic rats were treated with the vanadium complex (5 mg/kg body weight/day) for a period of 30 days and at the end of the treatment period the status of the lipid profile in the plasma, liver and kidney was evaluated. Also the fatty acid composition of liver and kidney were analysed by gas chromatography. The increased levels of lipid contents in plasma and tissues observed in diabetic rats were reverted back to near normal levels by the administration of the vanadium complex. Also the decreased levels of HDL cholesterol and increased levels of LDL cholesterol in plasma of diabetic rats were restored to near normal levels by the treatment with the vanadium complex. The altered fatty acid composition in liver and kidney were restored by the treatment. The results enhance the claim for the macrocyclic binuclear oxovanadium complex as a potent anti-diabetogenic drug.

Keywords

hypolipidemic macrocyclic vanadium complex insulin-mimetic streptozotocin diabetes hyperlipidemia hypercholesterolemia dyslipidemia fatty acids 

Abbreviations

MBOV complex

macrocyclic binuclear oxovanadium complex

STZ

streptoztocin

LPL

lipoprotein lipase

HSL

hormone sensitive lipase

G6PD

glucose-6-phosphate dehydrogenase

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References

  1. 1.
    O’Brien T, Nguyeen TT, Zimmerman BR: Hyperlipidaemia in diabetes mellitus. Mayo Clin Proc 73: 969, 1998PubMedGoogle Scholar
  2. 2.
    McGarry JD: What if Minkowski had been ageusic? An alternative angle on diabetes. Science 258: 766–770, 1992PubMedGoogle Scholar
  3. 3.
    Ebara T, Hirano T, Mamo JC, Sakamaki R, Furukawa S, Nagano S, Takahashi T: Hyperlipidemia in STZ diabetic hamsters as a model for human insulin dependent diabetes mellitus: comparison to STZ diabetic rats. Metabolism 43: 299–305, 1994CrossRefPubMedGoogle Scholar
  4. 4.
    Boyd DW, Kustin K: Vanadium: A versatile biochemical effector with an elusive biological function. Adv Inorg Biochem 6: 311–365, 1984PubMedGoogle Scholar
  5. 5.
    Heyliger EC, Tahiliani GA, McNeill JH: Effect of vanadate on elevated blood glucose and depressed cardiac performance of diabetic rats. Science 227: 1474–1477, 1985PubMedGoogle Scholar
  6. 6.
    Sakurai H, Tsuchiya K, Nukatsuka M, Sofue M, Kawada J: Insulin-like effect of vanadyl ion on streptozotocin diabetic rats. J Endocrinol 124: 451–459, 1990Google Scholar
  7. 7.
    Ramanadham S, Mongold JJ, Brownsey RW, Cors GS, McNeill JH: Oral vanadyl sulphate in treatment of diabetes mellitus in rats. Am J Physiol 257: H904–H911, 1989PubMedGoogle Scholar
  8. 8.
    Sekar N, Kanthasamy S, William S, Subramanian S, Govindasamy S: Insulinic action of vanadate on experimental diabetes. Pharmacol Res 22: 207–217, 1990PubMedGoogle Scholar
  9. 9.
    Nandhini D, Maneemegalai S, Elangovan V, Sekar N, Govindasamy S: Insulin like effects of bis-glycinato oxovanadium (IV) complex on experimental diabetic rats. Indian J Biochem Biophys 30: 73–76, 1993PubMedGoogle Scholar
  10. 10.
    Ramachandran B, Sathish Sekar D, Kandasamy M, Narayanan V, Subramanian S: Hypoglycemic effect of macrocyclic binuclear oxovanadium (IV) complex on streptozotocin induced diabetic rats. Exp Diabesity Res 5: 137–142, 2004CrossRefPubMedGoogle Scholar
  11. 11.
    Nanda KK, Mohanta SK, Ghosh S, Monika M, Helliwell M, Nag K: Macrocyclic mononuclear VIV and VV, heterodinuclear VV NiV and heterodinuclear VIV Ni II VV complexes: Synthesis, structure, electrochemistry and magneto chemistry. Inorg Chem 34: 2861–2869, 1995CrossRefGoogle Scholar
  12. 12.
    Meyerovitch J, Farfel Z, Sack J, Schechter Y: Oral administration of vanadate normalizes blood glucose levels in streptozotocin treated rats. J Biol Chem 262: 6658–6662, 1987PubMedGoogle Scholar
  13. 13.
    Canepa ET, Llambias EBC, Grinstein M: Studies on regulatory mechanisms of heme biosynthesis in hepatocytes from normal and experimental-diabetic rats. Role of insulin. Biochem Cell Biol 68: 914–921, 1990PubMedGoogle Scholar
  14. 14.
    Folch J, Lees M, Slone Stanley GH: A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226: 497–509, 1957PubMedGoogle Scholar
  15. 15.
    Parekh AC, Jung DH: Cholesterol determination with ferric acetate – uranyl acetate and sulphuric acid - ferrous sulphate reagents. Anal Chem 42: 1423–1427, 1970CrossRefGoogle Scholar
  16. 16.
    Foster LB, Dunn RT: Stable reagents for determination of serum triglycerides by a colorimetric Hantzsch condensation method. Clin Chem 19: 338–340, 1973PubMedGoogle Scholar
  17. 17.
    Itaya K: A more sensitive and stable calorimetric determination of free fatty acids in plasma. J Lip Res 18: 663–665, 1977Google Scholar
  18. 18.
    Bartlett GR: Phosphorus assay by column chromatography. J Biol Chem 234: 466–468, 1959PubMedGoogle Scholar
  19. 19.
    Fiske CH, Subbarow Y: The colorimetric determination of phosphorus. J Biol Chem 66: 375–400, 1925Google Scholar
  20. 20.
    Burstein M, Scholnick HR: Precipitation of chylomicron and very low density protein from human serum with sodium lauryl sulphate. Life Sci 11: 177–184, 1972Google Scholar
  21. 21.
    Morrison WR, Smith LM: Preparations of fatty acid methyl esters and dimethylacetals from lipids with boron fluoride methanol. J Lipid Res 5: 600–607, 1964Google Scholar
  22. 22.
    Howard BV, Abbott WG, Beltz WF, Harper IT, Fields RM, Grundy SM, Taskinen MR: Integrated study of low density lipoprotein metabolism and very low density lipoprotein metabolism in non-insulin-dependent diabetes. Metabolism 36: 870–877, 1987PubMedGoogle Scholar
  23. 23.
    Choi JS, Yokozawa T, Oura H: Improvement of hyperlgycemia and hyperlipemia in streptozotocin-diabetic rats by a methanolic extract of Prumus davidiana stems and its main component,prunin. Planta Med 57: 208–211, 1991PubMedGoogle Scholar
  24. 24.
    Sharma SR, Dwivedi SK, Swarup D: Hypoglycemic, antihyperglycemic and hypolipidemic activities of Caesalpinia bonducella seeds in rats. J Ethnopharmacol 58: 39–44, 1997PubMedGoogle Scholar
  25. 25.
    Brichard SM, Ongemba LN, Girard J, Henquin JC: Tissue-specific correction of lipogenic enzyme gene expression in diabetic rats given vanadate. Diabetologia 37: 1065–1072, 1994PubMedGoogle Scholar
  26. 26.
    Pugazenthi S, Angel JF, Khandelwal RL: Effects of high sucrose diet on insulin-like effects of vanadate in diabetic rats. Mol Cell Biochem 122: 77–84, 1993PubMedGoogle Scholar
  27. 27.
    Starzl TE, Francavilla A, Halgrimson CG, Francavilla FR, Porter KA, Brown TH, Putnam CW: Surg Gynaecol Obstet 137: 179–199, 1973Google Scholar
  28. 28.
    Mogensen CE, Anderson MJF: Increased kidney size and glomerular filtration rate in early juvenile diabetes. Diabetes 22: 706–712, 1973PubMedGoogle Scholar
  29. 29.
    Ramachandran B, Ravi K, Narayanan V, Kandaswamy M, Subramanian S: Protective effect of macrocyclic binuclear oxovanadium complex on oxidative stress in pancreas of streptozotocin induced diabetic rats. Chem Biol Interact 149: 9–21, 2004PubMedGoogle Scholar
  30. 30.
    Schwarz K, Milne DB: Growth effects of vanadium in the rat. Science 174: 426–428, 1971PubMedGoogle Scholar
  31. 31.
    Ramachandran B, Kandasamy M, Narayanan V, Subramanian S: Insulin mimetic effects of macrocyclic binuclear oxovanadium complex on STZ-induced experimental diabetes in rats. Diabetes Obes Metab 5: 455–461, 2003PubMedGoogle Scholar
  32. 32.
    Khan BA, Abraham A, Leelamma S: Hypoglycemic action of Murrya koenigii (curry leaf), Brassica juncea (mustard); mechanism of action. Ind J Biochem Biophys 32: 106–108, 1995Google Scholar
  33. 33.
    Mitra SK, Gopumadhavan S, Muralidhar TS, Anturlikar SD, Sujatha MB: Effect of D-400, a herbomineral preparation on lipid profile, glycated hemoglobin and glucose tolerance in streptozotocin induced diabetes in rats. Indian J Exp Biol 33: 798–800, 1995PubMedGoogle Scholar
  34. 34.
    Al-Shamaony L, Al-Khazraji SM, Twaij HA: Hypoglycemic effect of Artenmisia herba alba 11. Effect of a valuable extract on some blood parameters in diabetic animals. J Ethnopharmacol 43: 167–171, 1994PubMedGoogle Scholar
  35. 35.
    Savage PJ: Cardiovascular complications of diabetes mellitus: What we know and what we need to know about their prevention. Ann Int Med 124: 123–126, 1996PubMedGoogle Scholar
  36. 36.
    Nikkila EA, Hormila P: Serum lipids lipoproteins in insulin-treated diabetes demonstration of increased high density lipoprotein concentrations. Diabetes 27: 1078–1086, 1978PubMedGoogle Scholar
  37. 37.
    Somogyi A: Diabetes mellitus and lipoproteins. Orv Hetil 134: 2371–2377, 1993PubMedGoogle Scholar
  38. 38.
    Betteridge DJ: Diabetes, lipoprotein metabolism and atherosclerosis. Br Med Bull 45: 285–311, 1989PubMedGoogle Scholar
  39. 39.
    Morita T, Imagawa T, Kanagawa A, Ueki H: Sodium orthovanadate increases phospholipase A2 activity in isolated rats fat pads: A role of phospholipase A2 in the vanadate-stimulated release of lipoprotein lipase activity. Biol Pharm Bull 18: 347–349, 1995PubMedGoogle Scholar
  40. 40.
    Ramachandran B, Ravi K, Narayanan V, Kandaswamy M, Subramanian S: Effect of macrocyclic binuclear oxovanadium complex on tissue defense system in streptozotocin induced diabetic rats. Clin Chim Acta 345: 141–150, 2004PubMedGoogle Scholar
  41. 41.
    Setton-Avraj CP, Sterin-Speziale NB: Renal phospholipid metabolism in STZ-induced diabetic rats. Kidney Blood Press Res 19: 128–135, 1996PubMedGoogle Scholar
  42. 42.
    Lemieux G, Moulin B, Davignon J, Huag YS: The lipid content of diabetic kidney of rat. Can J Physiol Pharmacol 62: 1274–1278, 1984PubMedGoogle Scholar
  43. 43.
    West KM: Hyperglycemia as a cause of long term complications. In: H. Keen, J. Jarret (eds). Complication of diabetes. Edward Arnold, London, 1982, pp 3–18Google Scholar
  44. 44.
    Gupta D, Raju J, Jayaprakash R, Baquer NZ: Change in the lipid profile, lipogenic and related enzymes in the livers of experimental diabetic rats: Effect of insulin and vanadate. Diabetes Res Clin Pract 46: 1–7, 1999PubMedGoogle Scholar
  45. 45.
    Stanely MP, Menon VP, Gunasekaran G: Hypolipidaemic action of Tinospora cordifolia roots in alloxan diabetic rats. J Ethnopharmacol 64: 53–57, 1999PubMedGoogle Scholar
  46. 46.
    Sekar N, Govindasamy S: Insulin mimetic role of vanadate on plasma membrane insulin receptors. Biochem Int 23: 461–466, 1991PubMedGoogle Scholar
  47. 47.
    Goldfine AB, Simonson DC, Folli F, Patti ME, Kahn CR: Metabolic effects of sodium metavanadate in humans with insulin-dependent and noninsulin-dependent diabetes mellitus in vivo and in vitro studies. J Clin Endocrinol Metab 80: 3311–3320, 1995PubMedGoogle Scholar
  48. 48.
    Holman RT, Johnson SB, Gerrard JM, Maner SM, Kapcho-Sandbeg S, Brown DM: Arachidonic acid deficiency in streptozotocin-induced diabetes. Proc Natl Acad Sci USA 80: 2375–2379, 1983PubMedGoogle Scholar
  49. 49.
    Jones DB, Carter RD, Haitas B, Maan JI: Low phospholipid arachidonic acid values in diabetic platelets. Br Med J 286: 173–175, 1983Google Scholar
  50. 50.
    Tilvis RS, Helve E, Miettinen TA: Improvement of diabetic control by continuous subcutaneous insulin infusion therapy changes fatty acid composition of serum lipids and erythrocytes in type 1 diabetes. Diabetologia 29: 690–694, 1986PubMedGoogle Scholar
  51. 51.
    Cameron NE, Cotter MA: Effects of antioxidants on nerve and vascular dysfunction in experimental diabetes. Diabetes Res Clin Pract 45: 137–146, 1997CrossRefGoogle Scholar

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Balasubramanian Ramachandran
    • 1
    • 2
  • Sorimuthu Subramanian
    • 1
  1. 1.Department of BiochemistryUniversity of MadrasChennaiIndia
  2. 2.Department of BiochemistryUniversity of MadrasChennaiIndia

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