Amelioration of adriamycin-induced cardiotoxicity in rabbits by prenylamine and vitamins A and E

doi:10.1016/0002-8703(86)90559-4

American Heart Journal

Volume 111, Issue 1, January 1986, Pages 95-102

https://doi.org/10.1016/0002-8703(86)90559-4 Get rights and content

Abstract

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 < 0.05). Heart homogenates from ADM-treated rabbits showed an increased hydroperoxide-initiated chemiluminescence (expressed as cpm/mg protein × 10⁻³) of 77 ± 4 compared to control animals (52 ± 1) (p < 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.

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^☆: Supported by the National Research Council of Argentina and Fundación H. Pombo de Rodríguez.

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Amelioration of adriamycin-induced cardiotoxicity in rabbits by prenylamine and vitamins A and E☆

Abstract

Am Heart J

Lancet

Am Heart J

Arch Biochem Biophys

J Biol Chem

Chem Biol Interact

Am Heart J

Adriamycin and the heart

N Engl J Med

Electrolyte and morphologic alterations of myocardium in Adriamycin-treated rabbits

Am J Pathol

Overview of cardiac pathology in relation to anthracycline cardiotoxicity

Cancer Treat Rep

Adriamycin: The role of lipid peroxidation in cardiac toxicity and tumor response

Science

Prenylamine inhibition of Adriamycin-induced cardiomyopathy in mice

Medicina (B Aires)

Measurement of and protection from “in vivo” lipid peroxidation

Effect of selenium and vitamin E on adriamycin-induced cardiomyopathy in rabbits

Am J Vet Res

Failure of the antioxidant vitamin E to protect against Adriamycin-induced cardiotoxicity in the rabbit

Cancer Res

Experimental Adriamycin cardiotoxicity prevented by ubiquinone “in vivo” rabbits

Int Res Commun Syst Med Sci

Oxygen or organic hydroperoxide-induced chemiluminescence of brain and liver homogenates

Biochem J

Principles and methods for the morphometric study of the lung and other organs

Lab Invest

Influence of vitamin E and ICRF-187 on chronic doxorubicin cardiotoxicity in miniature swine

Lab Invest

Statistical methods of agricultural workers

An anthracycline antibiotic-induced cardiomyopathy in rabbits

Lab Invest

Prenylamine in angina pectoris

Ind Heart J