Amelioration of adriamycin-induced cardiotoxicity in rabbits by prenylamine and vitamins A and E.
The cardioprotective potentials of prenylamine (a calcium antagonist) and of a combination of vitamins A and E (a singlet oxygen quencher and a free radical scavenger, respectively) were evaluated in rabbits given chronically large doses of Adriamycin (ADM) (10.8 mg/kg body weight for 9 to 11 weeks). Among ADM-treated rabbits, 8 of 10 showed post-treatment ECG changes; in rabbits treated with ADM and prenylamine, changes were found in a smaller number (5 of 10); and in animals treated with ADM and vitamins A and E, the incidence was only one in six (p less than 0.05). Heart homogenates from ADM-treated rabbits showed an increased hydroperoxide-initiated chemiluminescence (expressed as cpm/mg protein X 10(-3)) of 77 +/- 4 compared to control animals (52 +/- 1) (p less than 0.01). Prenylamine administration did not alter hydroperoxide-initiated chemiluminescence in ADM-treated rabbits, whereas treatment with a combination of vitamins A and E showed a significant decrease in hydroperoxide-initiated chemiluminescence in control (40 +/- 2) and ADM-treated rabbits (42 +/- 1). Microscopically, myocardial fibers had mild to severe hydropic vacuolization of sarcoplasm, which led to progressive myocytolysis. A total of 103 +/- 13 damaged fibers were detected over 700 counted fibers. Myocardial damage was lowered to 47 +/- 16 by administration of prenylamine and to 28 +/- 8 by administration of vitamins A and E. It is suggested that ADM leads to myocardial lipid peroxidation (ameliorated by vitamins A and E) with membrane damage and to an increase in calcium permeability, the latter being counteracted by prenylamine.
D000818:Animals; D004317:Doxorubicin / Q000009:adverse effects*; D004357:Drug Synergism; D004562:Electrocardiography; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006333:Heart Failure / Q000139:chemically induced* / Q000188:drug therapy / Q000517:prevention & control; D006861:Hydrogen Peroxide / Q000378:metabolism; D008163:Luminescent Measurements; D008297:Male; D009206:Myocardium / Q000473:pathology; D011299:Prenylamine / Q000627:therapeutic use*; D011817:Rabbits; D014801:Vitamin A / Q000627:therapeutic use*; D014810:Vitamin E / Q000627:therapeutic use*
D014801:Vitamin A; D014810:Vitamin E; D004317:Doxorubicin; D006861:Hydrogen Peroxide; D011299:Prenylamine