Evaluation of cardiac effects of the new antineoplastic drug --dimethoxybenfluron--in the rabbit.
Cardiotoxicity ranks among the most serious adverse effects of some cytostatics. The cardiac effects of repeated i.v. administration of a new antineoplastic agent, dimethoxybenfluron (once a week, 10 administrations), were investigated in rabbits with respect to cardiac function and the release of cardiac troponin T (cTnT). Different doses of dimethoxybenfluron were administered to two groups of animals (12 mg/kg; n = 7 and 24 mg/kg; n = 6) and compared with either a control group (saline 1 ml/kg; n = 6) or a group with experimentally induced cardiomyopathy (daunorubicin 50 mg/m2; n = 13). In daunorubicin-induced cardiomyopathy, cTnT levels in animals with premature deaths were significantly higher (0.31 +/-0.11 microg/l) in comparison with the surviving animals (0.04 +/- 0.03 microg/l). However, cardiac TnT levels after the administration of dimethoxybenfluron in both doses were within the physiological range (lower than 0.1 microg/l) during the whole experiment as it was in the control group. The lack of cardiotoxicity of this new antineoplastic drug was supported by the absence of alterations in PEP:LVET ratio, left ventricle dP/dtmax or histological heart examination as well as by the fact that no premature death of animals occurred following repeated administration of dimethoxybenfluron. It is possible to conclude that no signs of cardiotoxicity were observed following repeated i.v. administration of dimethoxybenfluron.
Machacková
J
J
Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Králové, Czech Republic. machackovaj@lfhk.cuni.cz
Adamcová
M
M
Mazurová
Y
Y
Hrdina
R
R
Nobilis
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D003630:Daunorubicin; D005449:Fluorenes / Q000633:toxicity*; D006321:Heart / Q000187:drug effects*; D006331:Heart Diseases / Q000139:chemically induced* / Q000378:metabolism; D006439:Hemodynamics; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011817:Rabbits; D020107:Troponin T / Q000378:metabolism
C405005:3,9-dimethoxybenfluron; D000970:Antineoplastic Agents; D005449:Fluorenes; D020107:Troponin T; D003630:Daunorubicin