Current Issues of Pharmacy and Medical Sciences

Effect of thyroxine on cardiac GLUT4 changes in duced by doxorubicin

Current Issues in Pharmacy and Medical Sciences Vol. 26, No. 3, Pages 331-334

SLAWOMIR MANDZIUK1, URSZULA CZUBARA2, AGNIESZKA KORGA2, BARBARA MADEJ-CZERWONKA3,
MONIKA CENDROWSKA-PINKOSZ3, JAROSLAW DUDKA2

 
1Oncological Pneumology and Alergology Department, Medical University of Lublin, Lublin, Poland
2Medical Biology Unit, Medical University of Lublin, Lublin, Poland
3Department of Human Anatomy, Medical University of Lublin, Poland

DOI: 10.12923/j.2084-980X/26.3/a.20

 

Abstract

Doxorubicin is an efficient anticancer drug that causes a dose-dependent cumulative cardiotoxicity as one of the most serious side effects. This cardiotoxicity may develop for months or years leading to heart failure that is not curable. It is generally believed that the mechanism of these phenomena is followed by periodical, progressive oxidative damage in mitochondria triggered by doxorubicin. Serious disturbance in mitochondria may activate glycolysis as an alternative pathway to ATP synthesis. The fuel for this process is glucose, which is transported into cells via GLUT4. The objective of this study was to test the thesis that thy roxine modulates changes in cardiac expression of GLUT4 in rats re ceiv ing doxo ru bi cin. Rats were intraperitoneally treated with doxorubicin (1.5 mg/kg) once a week for ten weeks. Apart from doxorubicin, thyroxine was simultaneously given in drinking water (0.2 or 2.0 mg/l) for fourteen weeks. The study confirmed that doxorubicin increases cardiac concentration of mRNA and protein for GLUT4. Thyroxine had no sig nifi cant ef fect on mRNA and protein of GLUT4 changes induced by doxorubicin.

Files to download

Keywords

doxorubicin, throxine, GLUT4, heart

References

  1. Abdel-Aleem S et al.: Acute and chronic effects of adriamycin on fatty acids oxidation in isolated cardiac myocytes. J. Mol. Cell. Cardiol., 29; 789, 1997.
  2. Braunwald E, Zipes D, Libby P.: Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine, 2151-2171, Philadelphia 2001.
  3. Czarnecka A.M., et al.: Cancer as a mitochondriopathy. J. Cancer Mol., 3, 71, 2007.
  4. Delcers M, Goormaghtigh E.: Adriamycin effects on insulin secretion, Ca²+ movements and glucose oxidation in pancreatic islet cells. Pharmacol. Res. Commun., 17,  227, 1985.
  5. Doroshow J.H., Synold T.W., Somlo G.: Oxidative DNA base modifications in peripheral blood mononuclear cells of patients treated with high-dose infusional doxorubicin. Blood, 97, 2839, 2001.
  6. Geetha A, Catherine J, Shyamala Devi C.S.: Effect of alfa-tocopherol on doxorubicin induced alterations in glucose metabolism-A pilot study. J. Biosci., 14, 243, 1989.
  7. Holness MJ, Sugden MC.: Hepatic carbon flux after re-feed-ing. Hyperthyroidism blocks glycogen synthesis and the suppression of glucose output observed in response to carbohydrate re-feeding. Biochem J., 247, 627, 1987.
  8. Hrelia S. et al.: Doxorubicin induces early lipid peroxidation associated with changes in glucose transport in cultured cardiomyocytes. Biochimica et Biophysica Acta., 1569, 150, 2002.
  9. Hyyti O.M., et al.: Thyroid hormone controls myocardial substrate metabolism through nuclear recepto-mediated and rapid posttranscriptional mechanisms. Am. J. Physiol. Endocrinol. Metab., 290, E372-379, 2006.
  10. Kahn BB.: Glucose transport: pivotalstep in action. Lilly Lecture, Diabetes, 45, 1644, 1995.
  11. Loffer J., Blanc M.H.: Diabetes secondary to endocrine disease. Rev. Med. Siusse Romande.,  115, 721, 1995.
  12. Lombardi A., et al.: 3,5-diiodo-L-thyronine regulates glucose-6-phosphate dehydrogenase activity in the rate. Endocrinology, 141, 1729, 2000.
  13. Minotti G., et al.: Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol. Rev. 56, 185, 2004.
  14. Naskalski J.W., Dembińska-Kieć A.: Diagnostyka laboratoryjna z elementami biochemii klinicznej. Wrocław 2005; 401-405.
  15. Ogedegbe A.E.O., et al.: Hyperlactatemia syndrome associated with HIV therapy. Lancet, 3, 329, 2003.
  16. Pelicano H., Carney D., Huang P.: ROS stress in cancer calls and therapeutic implications. Drug Resist Updat., 7,  97, 2004.
  17. Singal P.K., Deally C.M., Weinberg L.E.: Subcellular effects of adriamycin in the heart: a concise review. J. Mol. Cell. Cardiol., 19, 817, 1987
  18. Stanley W.C., Beręsewicz A., Chandler M.P.: Metabilizm substratów energetycznych w normalnym i niewydolnym sercu i możliwości jego terapeutycznych modyfikacji. Kardiologia Polska, 53, 54, 2000.
  19. Tokarska-Schlattner M., et al.: New insights into doxorubicin-induced cardiotoxicity: The critical role of cellular energetics. J. Mol. Cell. Cardiol., 41, 389, 2006.
  20. Wallace K.B.: Doxorubicin-induced cardiac mitochondrionopathy. Pharmacol. Toxicol.; 93, 105, 2003.
  21. Weinstein S.P., et al.: Regulation of GLUT2 glucose transporter expression in liver by thyroid hormone: evidence for hormonal regulation of the hepatic glucose transport system. Endocrinology, 135, 649, 1994.
prev next

 

Calendar

April 2020

Mon Tue Wed Thu Fri Sat Sun
    01 02 03 04 05
06 07 08 09 10 11 12
13 14 15 16 17 18 19
20 21 22 23 24 25 26
27 28 29 30