Volume 50: 491-499, 2001

Evaluation of Cardiac Effects of the New Antineoplastic Drug - Dimethoxybenfluron - in the Rabbit

J. MACHÁČKOVÁ1, M. ADAMCOVÁ2, Y. MAZUROVÁ3, R. HRDINA4,
M. NOBILIS5

1Department of Pharmacology, 2Department of Physiology, and 3Department of Histology and Embryology, Charles University in Prague, Faculty of Medicine in Hradec Králové, 4Department of Pharmacology and Toxicology, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, 5Institute of Experimental Biopharmaceutics, Czech Academy of Sciences, Hradec Králové, Czech Republic


Received September 1, 2000
Accepted February 20, 2001


Summary
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 mg/l) in comparison with the surviving animals (0.04±0.03 mg/l). However, cardiac TnT levels after the administration of dimethoxybenfluron in both doses were within the physiological range (lower than 0.1 mg/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.


Key words
Cardiac troponin T · Daunorubicin · Dimethoxybenfluron · Cardiomyopathy · Antineoplastic drugs


Reprint requests
Macháčková Jarmila, M.Sc., Department of Pharmacology, Faculty of Medicine, Charles University, Šimkova 870, 500 01 Hradec Králové, Czech Republic, fax: 00420-49-5513597, e-mail: machackovaj@lfhk.cuni.cz


PHYSIOLOGICAL RESEARCH
© 2001 by the Institute of Physiology, Czech Academy of Sciences

ISSN 0862 - 8408

Issue 5