Estudo comparativo de antraciclicos na indução de cardiotoxicidade experimental manuscrito : parâmetros eletro e ecocardiográficos, marcadores bioquímicos, alterações morfo-funcionais e abordagem farmacológica

Abstract

A specific cardiotoxicity, wich develops with critica! cumulative doses of the anthracylcines, is the major limiting factor in the use of these agents in long-term treatments. Several animais models reproducing doxorubicin-induced morphological, biochemical and functional cardiac alterations have been described an used for screening of new analogs. In previous studies we desenvolved an in vivo doxorubicin schedule for the study of anthracycline induced cardiotoxicty in rats with which consistent and significant funcional and morphologic myocardial alterations can be observed and mensured in a relatively short time. The aim of the present study was to validate the proposed model for anthracycline-induced carditoxicity in the rat using the epirubin, idarubicin and mitoxantrone. Besides evaluating the cardioprotector potential of the thalidomide and pentoxifillyne.. The parameters used in this evaluation has been: Electrocardiogram (ECG) and Echocardiogram (ECO) changes, biochemicals markers, ponderai curve, hematologic values, cardiac, hepatic and splenic index and histological analysis. The analysis of the result had demonstrated that the epirubicin, idarubicin and mitoxantrone, when being used in cumulative doses seen to present carditoxicity like to doxorubicin. When we use markers of acute myocardial lesion as T troponin, CK-MB and LDH, not if they observe significant differences between these agents and doxorubicin. The pentoxifillyne and thalidomide one obtain to inhibit the induced cardiotoxicity for doxorubicin, epirubicin, idarubicin and mitoxantrone in the used model. Moreover the doxorubicin when mananged in exceeded doses, also it has its cardiotoxic potential inhibited by these two agents. Our recents studies suggest that in the used model of experimental cardiotoxicity few differences between the cardiotoxic potential presented by diverse anthracyclics analogs exist and this can be inhibited by pentoxifillyne and thalidomide, that can to be used in the clinic as cardioprotective agents.