Biological Trace Element Research

, Volume 89, Issue 3, pp 215–226

Protective effect of selenium treatment on diabetes-induced myocardial structural alterations

  • Murat Ayaz
  • Belgin Can
  • Semir Ozdemir
  • Belma Turan
Article

Abstract

One of the main causes leading to mortality in diabetes is myocardial disease. Using streptozotocin (STZ)-induced diabetic animals, it has been possible to characterize diabetes-induced myocardial abnormalities. Interstitial and microvascular disorders are known to be a characteristic part of the diabetic cardiomyopathy and partly resist insulin therapy. Because diabetic damage is partly attributed to oxidative stress, antioxidant treatment may be able to reduce this damage. The aim of this study was to investigate the cardioprotective effect of sodium selenite, known as an antioxidant agent. The diabetes was induced by ip injection of 50 mg/kg body wt STZ. The duration of diabetes was 5 wk. The protected group received (ip) 5 µmol/kg body wt/d sodium selenite (Na2SeO3) over 4 wk following diabetes induction. Electron and light microscopic morphometry of heart samples revealed typical diabetic alterations consisting in an increase in collagen content, vacuolation, diminishing of the cardiomyocyte diameter, alteration in myofilaments and Z-lines of myofibers, and myofibrillary degeneration. Sodium selenite treatment could prevent the loss of myofibrills and reduction of myocyte diameter. In the sodium-selenite-treated diabetic rat heart, alterations of the discus intercalaris and nucleus were corrected, and degenerations seen in myofilaments and Z-lines were reversed by this treatment. Under these findings, one can suggest that sodium selenite treatment may alleviate late diabetic complications when it is used under control conditions.

Index Entries

Sodium selenite heart histology ultrastructure diabetes rat 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    W. B. Kannel, M. Hjortland, W. P. Castelli, Role of diabetes in congestive heart failure: the Framingham study,Am. J. Cardiol. 34, 29–35 (1974).PubMedCrossRefGoogle Scholar
  2. 2.
    T. J. Regan, M. M. Lyons, S. S. Ahmed, G. E. Levinson, H. A. Oldewurtel, M. R. Ahmed, et al., Evidence for cardiomyopathy in familial diabetes mellitus,J. Clin. Invest. 60, 885–899 (1977).CrossRefGoogle Scholar
  3. 3.
    R. R. Mildenberger, B. Bar-Shlomo, M. N. Druck, G. Jablonsky, J. E. Morch, J. D. Hilton, et al., Clinically unrecognized ventricular dysfunction in young diabetic patients,J. Am. Coll. Cardiol. 4, 234–238 (1984).PubMedCrossRefGoogle Scholar
  4. 4.
    J. Eckel and H. Reinauer, Insulin action on glucose transport in isolated cardiac myocytes: signalling pathways and diabetes-induced alterations,Biochem. Soc. Trans. 18, 1125–1127 (1990).PubMedGoogle Scholar
  5. 5.
    W. T. Garvey, D. Hardin, M. Juhaszova, and J. H. Dominguez, Effects of diabetes on myocardial glucose transport system in rats: implications for diabetic cardiomyopathy,Am. J. Physiol. Heart Circ. Physiol. 264, H837-H844 (1993).Google Scholar
  6. 6.
    R. I. Hamby, S. Zoneraich, and S. Sherman, Diabetic cardiomyopathy,JAMA 229, 1749–1754 (1974).PubMedCrossRefGoogle Scholar
  7. 7.
    O. Gotzsche, Myocardial cell dysfunction in diabetes mellitus,Diabetes 35, 1158–1162 (1986).PubMedCrossRefGoogle Scholar
  8. 8.
    J. J. Friedman, Vascular sensitivity and reactivity to norepinephrine in diabets mellitus,Am. J. Physiol. 256, H1134-H1138 (1989).PubMedGoogle Scholar
  9. 9.
    T. Ledet, Diabetic cardiomyopathy: quantitative histological studies of the heart from young juvenile diabetics,Acta Pathol. Microbiol. Scand. 84, 421–428 (1976).Google Scholar
  10. 10.
    G. N. Pierce, M. J. B. Kutryk, and N. S. Dhalla, Alterations in Ca++ binding by and composition of the cardiac sarcolemmal membrane in chronic diabetesProc. Natl. Acad. Sci. USA 80, 5412–5416 (1983).PubMedCrossRefGoogle Scholar
  11. 11.
    S. Penpargkul, F. S. Fein, E. H. Sonnenblick, and J. Scheuer, Depressed cardiac sarcoplasmic reticular function from diabetic rats,J. Mol. Cell. Cardiol. 13, 303–309 (1981).PubMedCrossRefGoogle Scholar
  12. 12.
    G. N. Pierce and N. S. Dhalla, Cardiac myofibrillar ATPase activity in diabetic rats,J. Mol. Cell. Cardiol. 13, 1063–1069 (1981).PubMedCrossRefGoogle Scholar
  13. 13.
    A. Malhotra and V. Sanghi, Regulation of contractile proteins in diabetic heart,Cardiovasc. Res. 34, 41–47 (1977).Google Scholar
  14. 14.
    G. Fitzl, R. Martin, D. Dettmer, V. Hermsdorf, and K. Welt, Protective effects of Gingko biloba extract Egb 761 on myocardium of experimentally diabetic rats. Ultrastructural and biochemical investigation on cardiomyocytes,Exp. Toxicol. Pathol. 51(3), 189–198 (1999).PubMedGoogle Scholar
  15. 15.
    K. Welt, J. Weiss, S. Koch, and G. Fitzl, Protective effects of Ginkgo biloba extract Egb 761 on the myocardium of experimentally diabetic rats. II. Ultrastructural and immunohistochemical investigation on microvessels and interstitium,Exp. Toxicol. Pathol. 51(3), 213–222 (1999).PubMedGoogle Scholar
  16. 16.
    J. W. Baynes, Role of oxidative stress in development of complications in diabetes,Diabetes 40, 405–412 (1991).PubMedCrossRefGoogle Scholar
  17. 17.
    J. W. Baynes and S. R. Thorpe, Role of oxidative stress in diabetic complications: a new perspective on an old paradigm.Diabetes 48, 1–9 (1999).PubMedCrossRefGoogle Scholar
  18. 18.
    C. E. Heyligir, A. G. Tahiliani, and J. E. McNeill, Effect of vanadate on elevated blood glucose and depressed cardiac performance of diabetic rats,Science 227, 1474–1476 (1985).CrossRefGoogle Scholar
  19. 19.
    S. M. Brichard, W. Okitolonda, and J. C. Henquin, Long term improvements of glucose homeostasis by vanadate treatment in diabetic rats,Endocrinology 123, 2048–2053 (1988).PubMedCrossRefGoogle Scholar
  20. 20.
    M. Bendayan, and D. Gingars, Effect of vanadate administration on blood glucose and insulin levels as well as on the exocrine pancreatic function in streptozotocin-diabetic rats,Diabetologia 32, 561–567, (1989).PubMedCrossRefGoogle Scholar
  21. 21.
    Y. Shechter, Insulin-mimetic effects on vanadate. Possible implications for future treatment of diabetes,Diabetes 1, 1–5 (1990).CrossRefGoogle Scholar
  22. 22.
    C. Fillat, J. E. Rodriguez-Gil, and J. J. Guinovart, Molybdate and tungstate act like vanadate on glucose metabolism in isolated hepatocytes,Biochem. J. 282, 659–663 (1992).PubMedGoogle Scholar
  23. 23.
    M. C. Munoz, A. Barbera, J. Dominguez, J. Fernandez-Alvarez, R. Gomis, and J. J. Guinovart, Effects of tungstate, a new potential oral antidiabetic agent, in zucker diabetic fatty rats,Diabetes 50, 131–138 (2001).PubMedCrossRefGoogle Scholar
  24. 24.
    L. J. Coppey, J. S. Gellett, E. P. Davidson, J. A. Dunlap, D. D. Lund, and M. A. Yorek, Effect of antioxidant treatment of streptozotocin-induced diabetic rats on endoneurial blood flow, motor nerve conduction velocity, and vascular reactivity of epineurial arterioles of the sciatic nerve,Diabetes 50, 1927–1937 (2001).PubMedCrossRefGoogle Scholar
  25. 25.
    E. I. Tolman, E. Barris, M. Burns, R. Pansini, and R. Partridge, Effects of vanadium on glucose metabolism in vitro,Life Sci. 25, 1159–1165 (1979).PubMedCrossRefGoogle Scholar
  26. 26.
    O. Ezaki, The insulin-like effects of selenate in rat adipocytes,J. Biol. Chem. 265, 1124–1130 (1990).PubMedGoogle Scholar
  27. 27.
    J. H. McNeill, H. L. M. Delgatty, and M. L. Battell, Insulinelike effects of sodium selenate in streptozotocin-induced diabetic rats,Diabetes 40, 1675–1678 (1991).PubMedCrossRefGoogle Scholar
  28. 28.
    G. Berkenboom, D. Brekine, Z. Y. Fang, J. Neve, and J. Fontaine, Prevention by selenium supplementation of cyclosporin-A-induced vascular toxicity.Cardiovasc. Res. 33, 650–654 (1997).PubMedCrossRefGoogle Scholar
  29. 29.
    E. A. Berg, J. Y. Wu, L. Campbell, M. Kagey, and S. R. Stapleton, Insulin-like effects of vanadate and selenate on the expression of glucose-6-phosphate dehydrogenase and fatty acid synthase in diabetic rats,Biochimie 77, 919–924 (1995).PubMedCrossRefGoogle Scholar
  30. 30.
    D. J. Becker, B. Reul, A. T. Ozcelikay, J. P. Buchet, J. C. Henquin, and S. M. Brichard, Oral selenate improves glucose homeostasis and partly reverses abnormal expression of liver glycogenic and gluconeogenic enzymes in diabetic rats,Diabetologia 39, 3–11 (1996).PubMedCrossRefGoogle Scholar
  31. 31.
    M. L. Battell, H. L. M. Delgatty, and J. H. McNeil, Sodium selenate corrects glucose tolerance and heart function in STZ diabetic rat adipocytes,Mol. Cell. Biochem. 179, 27–34 (1998).PubMedCrossRefGoogle Scholar
  32. 32.
    C. Gocmen, A. Secilmis, E. K. Kumcu, P. U. Ertug, S. Onder, A. Dikmen, et al., Effects of vitamin E and sodium selenate on neurogenic and endothelial relaxation of corpus cavernosum in the diabetic mouse,Eur. J. Pharmacol. 398, 93–98 (2000).PubMedCrossRefGoogle Scholar
  33. 33.
    N. Takeda, I. M. Dixon, T. Hata, V. Elimban, K. R. Shah, and N. S. Dhalla, Sequence of alterations in subcellular organelles during the development of heart dysfunction in diabetes,Diabetes Res. Clin. Pract. 30(Suppl.), 113–122 (1996).PubMedCrossRefGoogle Scholar
  34. 34.
    N. S. Dhalla NS, Liu X, Panagia V. et al. Subcellular remodeling and heart dysfunction in chronic diabetes.Cardiovasc. Res. 40(2), 239–47 (1998).PubMedCrossRefGoogle Scholar
  35. 35.
    V. Di Bello, O. Giampietro, E. Matteucci, et al., Ultrasonic tissue characterization analysis in type 1 diabetes: a very early index of diabetic cardiomyopathy,G. Ital. Cardiol. 28(10), 1128–1137 (1998).PubMedGoogle Scholar
  36. 36.
    J. Ren and A. J. Davidoff, Diabetes rapidly induces contractile dysfunctions in isolated ventricular myocytes,Am. J. Physiol. 272(1 Pt 2), H148-H158 (1997).PubMedGoogle Scholar
  37. 37.
    E. I. Sokolov, O. S. Zaichikova, and V. G. Tsyplenkova, Ultrastructure of the myocardium in patients with cardiac pathology complicated by diabetes mellitus,Arkh. Patol. 60(1), 49–54 (1998).PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2002

Authors and Affiliations

  • Murat Ayaz
    • 1
  • Belgin Can
    • 2
  • Semir Ozdemir
    • 1
  • Belma Turan
    • 1
  1. 1.Department of BiophysicsAnkara UniversityAnkaraTurkey
  2. 2.Department of Histology-Embryology, Faculty of MedicineAnkara UniversityAnkaraTurkey

Personalised recommendations