ABSTRACT
Doxorubicin (DOX) is one of the most effective anti-cancer drugs in oncology, but may cause a cumulative dose-dependent cardiomyopathy in a number of cancer patients. The effect of DOX on the heart was studied in mice treated with i.v. injections of 2 mg/kg by measuring morphometric parameters, including nuclear index (number of non-myocytes/number of myocyte nuclei), reticulin index (reticulin area/number of myocyte transsections), nuclear transsectional area, myocyte transsectional area, capillary index (number of capillaries/number of myocyte transsections) and capillary transsectional area. The highest significant difference between control mice and DOX-treated mice was observed immediately after the 12th dose of DOX except for the two capillary parameters. The highest level of significance for these two parameters was obtained 12 weeks after the end of DOX treatment. In contrast to the observations in rats, mice did not develop a nephrotic syndrome during treatment with DOX. The morphometric analysis of myocardial changes in mice, as a quantitative and objective method, seems to be a good model for comparative studies on cardiomyopathy induced by anthracycline analogues.
Subject(s)
Cardiomyopathies/chemically induced , Doxorubicin/adverse effects , Myocardium/pathology , Animals , Body Weight/drug effects , Capillaries/pathology , Cardiomyopathies/pathology , Cardiomyopathies/urine , Cell Nucleus/pathology , Female , Mice , Proteinuria/pathology , Reticulin/analysis , Time FactorsABSTRACT
Puromycin aminonucleoside (PAN)-treated rats developed a severe nephrotic syndrome. Morphometric analysis of the hearts revealed significant differences between treated and control rats regarding nuclear index, reticulin index, nuclear and myocellular transsectional area, capillary number and transsectional area of capillaries. These differences were comparable with those induced by adriamycin. It is suggested that PAN can induce morphometrically measurable abnormalities in hearts of rats comparable to the morphometric changes seen after adriamycin treatment. The question of whether nephropathy, a result of both DOX and PAN treatment of rats, adds to or perhaps even causes doxorubicin - induced cardiomyopathy remains unclear.
