[The prevention of the myocardial toxicity of doxorubicin with superoxide dismutase].
The production of oxygen free radicals during anthracycline therapy has been proposed as a determinant of the toxicity of anthracyclines. Oxygen radical generation might specifically affect the myocardium because of the low antioxidant defense systems in cardiac tissue. The aim of the present investigations was to evaluate the potential cardioprotective effect of superoxide dismutase (SOD) against the delayed cardiomyopathy induced by doxorubicin (DXR) in a rat model. Female Sprague Dawley rats received 3 mg/kg of DXR intravenously weekly for 4 weeks. SOD was administered intravenously at the dose of 10,000 U/Kg one minute before and 30 minutes after each DXR administration. Cardiac toxicity was monitored in vivo by means of electrocardiography (QaT interval), by determining the contractile properties of isolated atria, and by light and electron microscopy evaluation of left ventricle fragments excised 5 weeks after the last DXR administration. The degree of morphologic lesions was quantitated according to the score system proposed by E. Billingham. DXR treated rats showed, in comparison with control animals treated with saline a decrease of body weight gain, a progressive and irreversible prolongation of QaT, decrease of contractility of isolated atria, and significant morphologic lesions consisting in myocyte vacuolization and myofibrillar loss. SOD significantly prevented the impairment of body weight gain, QaT prolongation and the impairment of myocardial contractility. Moreover morphologic lesions were significantly reduced in rats receiving DXR + SOD. The present data indicate that SOD could represent an important issue in myocardial protection against DXR cardiotoxicity.
Villani
F
F
Divisione di Fisopatologia Cardiorespiratoria, Istituto Nazionale per lo Studio e la Cura dei Tumori di Milano.
Galimberti
M
M
Favalli
L
L
Rozza
A
A
Lanza
E
E
Poggi
P
P
D000818:Animals; D004317:Doxorubicin / Q000633:toxicity*; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D004361:Drug Tolerance; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000627:therapeutic use*; D013997:Time Factors
D004317:Doxorubicin; D013482:Superoxide Dismutase
Prevenzione della tossicità miocardica da doxorubicina con superossido dismutasi.