Effect of thyroxine on cardiac GLUT4 changes in duced by doxorubicin

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.